Its been a month since the United States Federal Drug Administration (FDA) rejected Lykos Therapeutics novel drug application for MDMA-assisted therapy as a treatment for post traumatic stress disorder (PTSD) on August 11, 2024.

Between the FDA public advisory meeting and this decision, Lykos and MAPS hired public relations firms and partnered with Heroic Hearts Project, among other organizations, to launch a large campaign in attempts to push forward FDA approval. This campaign included highlighting that many veterans will commit suicide while the FDA Ad-Comm rejected safety and efficacy of MDMA-AT, as well as calling for more donations to MAPS. Part of this campaign also included hateful speech from the Heroic Hearts Project singling out a specific member of Psymposia who chose to speak out against Lykos protocols. This post has since been taken down, but a response by Dr. Peter H. Addy, former VA research psychologist, still is available and highlights some of this response.

Lykos and MAPS also issued their own petition, calling for experts to endorse MDMA-AT, which gained 26 signatories. Of these 26 signatories, 12 are involved with the sponsor or MAPS. This is a contrast to the petition that was filed to the FDA calling for the public ad-comm meeting and encouraging the FDA to pay attention to misconduct of the sponsor organization. This petition received over 80 signatures, of which 50% were experts in trauma-related disorders, psychology, psychedelic and/or patient advocates. Under 10 of these signatories were involved in other groups such as Psymposia.

In August, despite the PR campaign and a bi-partisan political effort, the FDA officially rejected Lykos’ application with a call for more rigorous Phase 3 Clinical Trials. This was a large surprise to almost everyone, as polls suggested that many thought FDA would approve with post-approval monitoring. This decision led to a dumpster fire, including the throwing of blame filled Molotov cocktails. Adding accidental fuel only 24 h following the decision, the official journal of the European Behavioral Pharmacology Society, Psychopharmacology, retracted three articles related to Lykos clinical trials, including data from four phase two trials (Feduccia et al, 2021). This came after multiple efforts and letters by independent journalist Sasha Sisko. In the aftermath, Lykos has undergone a complete personnel reorganization, including the resignation founder Rick Doblin from the Board, resignation of their CEO Amy Emerson, and layoff of over 75% of staff. They also have brought on David Hough, former Janssen executive, as senior medical advisor.

There is no need to dive deeper into the explosive aftermath from the FDA decision, as it has been extensively reported and all over the internet. The rest of this article will focus primarily on how to move forward, highlighting the other opportunities to further psychedelic medicine.

There are several other groups working to further psychedelic science and psychedelic-assisted therapy (including MDMA). Lykos Therapeutics is not the only organization seeking FDA approval for MDMA-AT or developing MDMA and related compounds for mental health. Tactogen, Arcadia, Terran, Mindmed and others are actively working towards this as well. Just this week, Clearmind Medicine — a clinical-stage psychedelic pharmaceutical biotech out of Vancouver, Canada — recently announced an international patent application for its combination of MDMA with N-Acylethanolamines (NAEs). This is the thirteenth patent application associated with this line of work, but as we know, patent applications don’t necessarily mean progress on clinical use and accessibility of these compounds.

Outside of these companies, many publicly funded universities and organizations without pharmaceutical interests are also progressing on understanding psychedelics and other pharmacological interventions and how they can be useful for treatment of trauma-related disorders. This includes work at University of Calgary, Johns Hopkins University, Emory University, and more. According to clinicaltrials.gov, there are currently 477 studies recruiting/not yet recruiting related to studying PTSD.

Regulatory Agency Interest

Regulatory agencies have not stopped conversations about next steps regarding novel therapeutics for PTSD. Just this past week, the Reagan-Udall Foundation for the Food and Drug Administration, an independent 501(c)(3) organization created by Congress, hosted a hybrid event titled, “Advancing Treatments for Post-Traumatic Stress Disorder.”

This event had opening remarks by Dr. Bernard A. Fischer, Deputy Director of Office of New Drugs Center for Drug Evaluation and Research, FDA, which featured a brief history of PTSD and symptomatology, as well as where we are in terms of current research and drug development. He highlighted there are currently two approved pharmacotherapies for PTSD, sertraline and paroxetine, both of which are selective serotonin reuptake inhibitors (SSRIs). Dr. Fischer also shared information about an approved medical device, Nightware, which is used to temporarily reduce sleep disturbance related to nightmares in adults 22 years or older who have been diagnosed with nightmare disorder or have nightmares from PTSD.

In the end of his introduction, he gave some advice from the FDA. First, he emphasized the need to have a representative sample in research. This was not only about demographics, but also of the disease itself, including a range of times since the traumatic event, variety of events, and single vs. repeated events. Dr. Fischer then went on to discuss how the field is actually quite well-suited to understand PTSD from a neuroscience point-of-view, and that future studies should build from what we know, instead of trying to reinvent the wheel.

“There are not a lot of good animal models to understand mental health conditions, but this response to threat circuit [related to PTSD] that I’ve talked about can be modeled in animals.”

Given the uniqueness of neuropsychiatric symptoms across individuals, a lot of research is also being done with genetic biomarkers. These may be able to help determine who is at risk for developing PTSD and maybe in the future used to help diagnose PTSD or determine whether people with PTSD will respond to a certain treatment.

Finally, he discussed how looking at resilience studies of people without PTSD may be able to better inform development of novel therapeutics. Specifically, focusing on what can be taught from people who experience traumatic events and don’t end up developing PTSD.

In addition to these remarks, this event featured a panel of prominent voices in the regulatory space including: Dr. Elyse Katz of the Department of Defense, Dr. Leith J. States of the Office of the Assistant Secretary for Health within HHS, Dr. Neeraj ‘Jim’ Gandotra of the Substance Abuse and Mental Health Services Administration (SAMHSA) within HHS, Dr. Marta Sokolowska of the FDA within HHS, and Dr. Paula P. Schnurr and Dr. Miriam J. Smyth of the US Department of Veterans Affairs. There comments will be summarized below.

SAMHSA

Dr. Gandotra discussed some important work going on at SAMHSA as it relates to PTSD. The overall goal of this organization is to be able to provide resources for evidence-based interventions that balance the therapeutic efficacy but also the risks associated with interventions.

“Our strategic plan is underpinned by the principles of equity, trauma-informed approaches and committment to data and recovery. We feel that all of those cross-cutting principles must be addressed in everything we do.” -Dr. Gandotra

The projects that SAMHSA has been working on related to PTSD include projects focused on suicide prevention. First being the 988 crisis lifeline, which is a number that can be dialed or texted for immediate intervention for someone with suicidal ideation or plan. Dr. Gandotra praised this line, which has been “a tremendous resource for under-resourced communities” and has been very useful in linking people to care.

Another program Dr. Gandotra highlighted is their technical service program, ReCAST: Resiliency in Communities After Stress and Trauma. This program has trained over 100,000 mental health workers and community members, as well over 950 partner organizations. He also discussed that PTSD can be initiated and emerge in childhood and as such, they have a program specifically for children, National Child Traumatic Stress Initiative. The initiative has served over 1 million people and includes resources for collaboration among the community.

“While we can sit in DC and come up with policies, its the programs out in the communities that implement these policies and we don’t know what we don’t know. We have to get feedback from those grantees, from those individuals who are serving the communities that we hope benefit from our resources.” — Dr. Gandorta

Department Of Defense

Dr. Katz, contractor supporting the DOD Health Agencies PTSD Program, discussed a clinical trial happening through the DOD. She shares the objective of their PTSD drug treatment program is to develop drugs that effectively treat PTSD, taking into account high quality evidence for or against use of existing drugs and by partnering or supporting industry development programs to increase chances of approval of novel drugs.

Dr. Katz shared her thoughts on the recent developments in novel treatment for PTSD,

“We believe much of the failure in this area is due to the lack of fully understanding the clinical and biological differences between individuals with PTSD, as well as due to a siloed research approach in the area that includes the conduct of small one-off studies from individual investigators or companies with unique testing procedures and endpoints. — Dr. Katz

She went on to share how the DOD program aims to address these issues. This program has partnered with organizations across disciplines and industries to create a PTSD Adaptive Platform Trial, which is the first of its kind in psychiatry. This study design is unique in that it allows sharing of placebo data across arms, as well as testing multiple drugs at the same time. The idea is that the drugs being tested will cycle off the platform based on evidence for their probability of success or failure for decreasing PTSD symptoms. This trial is currently testing two drugs in the FDA-regulated Phase 2 Master Protocol and 4 other drugs, including an intranasal racemic ketamine formulation.

Dr. Katz also discussed the collection of biomarker data and several clinical assessments, hoping to tease apart the heterogeneity of individuals with PTSD. The goal of this research is to lead to a precision medicine approach where drugs are prescribed based on what would be most effective for the individual. The website for this study will be live in the coming weeks: ptsdclinicaltrial.org

Veteran Affairs

To begin, Dr. Schnurr shared the top priority of the VA is providing the safest, most effective care available for the nations veterans. The VA approach prioritizes recovery through evidence based treatment across continuum of care , which includes access to everything from self help apps to acute care to residential treatment. The VA also collaborates with with the DOD to determine appropriate clinical practice guidelines for both mental and physical conditions relevant to population.

As the executive director of National Centers for PTSD, Dr. Schnurr shared advancements in groundbreaking research related to intervention, medication, psychotherapy and even integrative practices (e.g yoga) that have led to creating gold standards in assessments, questionnaires and interviews for PTSD.

The VA has also sponsored a large practitioner training program for providers that teaches evidence based psychotherapy for PTSD using two of the most effective treatments: prolonged exposure therapy and cognitive processing therapy. All VA medical centers offer these treatments and have trained professionals in other evidence based treatments to encourage folks to seek treatment. Dr. Katz promoted that the VA is also preparing to implement psychedelic-assisted therapy for PTSD when the evidence is enough for FDA approval.

“First of all PTSD is treatable condition, I think that sometimes we don’t hear that. PTSD is a treatable condition. There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response for improvement. This isn’t just a PTSD problem, its a mental health disorder problem. This is why at the VA is committed to supporting innovations for PTSD and other mental disorders, which includes psychedelic medicine. At VA, we are preparing for future potential clinical implementation of psychedelic treatment, primarily by supporting and conducting research on medications such as MDMA and psilocybin for treating PTSD and depression.” -Dr. Katz

Dr. Smyth of the VA built on the comments related to innovative research, sharing how the VA is involved in over 140 active research projects and have 230 million dollars invested in this research. She highlighted three programs:

1. The PTSD Psychopharmacology Initiative. Active since 2017, the goal of this initiative is to provide better treatments for veterans by broadening psychopharmacology clinical trials workforce. The first trial under this intiative is ending in 2024 and results will be published accordingly.
2. The Million Veteran Program. This is a novel national research program looking at how genes, lifestyle, military experiences and exposures effect health and wellness of veterans. There are 1.5 million participants enrolled in this program. To date, studies have found genes related to re-experiencing traumatic memories and advanced understanding the relationship between PTSD, TBI and dementia. Specifically, they have found evidence of PTSD and TBI as risk factors for developing dementia in this population.
3. Psychedelic Medicine. The VA shared their first request for applications related to psychedelic research in 2024. They are primarily interested in testing MDMA and psilocybin in combination with psychotherapy for PTSD and depression in veterans.

Dr. Smyth shared that while some studies related to psychedelics have occurred at VA sites across the country these were funded by external organization with overall small veteran enrollment. She shared decisions related to VA funding will be made this fall. “In the meantime,” she said, “We remind veterans for their safety, they should not use psychedelics as part of a self-treatment program.”

FDA

Dr. Sokolowska discussed the role of the FDA in reviewing applications related to novel treatments and medical devices. The main responsibility of the FDA is to ensure a drug is both safe and effective, which is done by reviewing the data and information provided in the application of the sponsors.

The FDA has approved two medications for PTSD, but they understand the great need for better treatments. With that, Dr. Sokolowska added, the FDA has the breakthrough status program in which they have granted breakthrough status for MDMA for treatment of PTSD. She also highlighted the FDA has done a lot in terms of approving marketing authorization of medical devices related to PTSD. This includes the approval of Nightware in 2020, as mentioned above. Recently, Prism Technology was approved to be marketed as adjunct treatment for PTSD to help patients self-regulate symptoms.

HHS

Dr. States, who works within the Office of the Assistant Secretary for Health of Human Health and Services, opened by acknowledging that PTSD doesn’t happen in isolation and there are many factors that won’t be solved by a seminar or single drug-application.

He discussed the importance of remembering there are co-morbid mental health and behavioral considerations, but also impacts of generational trauma, food insecurity, and issues in accessibility to treatments that contribute to baseline individual level of distress and inability to comply to a treatment regime. The available treatments, and even novel treatments, very well may be founded on good sound base of evidence, but because of those other considerations they’re not going to get the full effectiveness in the entire population.

He had a unique response to what comes next for innovative treatments, speaking to the “relative lack of innovation in the space”,

“…its not just that we need to get more tools, but we need to learn how to use adequately and respond to the environment were currently operating in. There is no silver bullet. The hard work of getting to change is what is taking place here today….We all feel some type of way about the decision that came out sometime ago, and that’s alright. We’re all big kids in the room, thats okay. For me, its indicative of a fact that were pushing forward and were stressing the system in a way that marches us forward in an incremental way. Now, granted, there might be some dissonance about what we thought was appropriate levels of evidence of this or that, but regardless of this, at the end of the day I see opportunity.” — Dr. States

Dr. States went on to say he believes the opportunity is in understanding that solution is not just in NDAs and the FDA sharing the burden alone, its about collaboration and developments across the various regulatory agencies and the increased opportunities for representative data, novel trial design and time needed to adjust to the rapidly evolving changes in approach to randomized clinical trial design.

He ended with suggesting a shift in focus to pivot beyond clinical trials and NDAs, to acknowledge the landscape in which were operating in, which includes looking toward state, local, tribal and territorial governments. By interacting and embracing these places and programs that are moving forward, there is an opportunity to collect data that could be informative to the health and safety of the American people.

Stakeholder Interest

In a similar vein to the FDA Ad-Comm meeting, this sponsored event also included a public stakeholder comment section. The comment period consisted of 75 minutes of public commentary, which each commenter was given 3 minutes to share their thoughts. Considering the overlap in the commentary of this event and the FDA Ad-Comm meeting, this section will highlight a select number of commentary from several viewpoints and from those with organizations that are moving forward with psychedelic-assisted therapy based approaches.

Dr. Michael Abrams, representative of a consumer advocacy organization. He began with a brief overview of the adequacy of various therapies, including psychedelic-AT. Dr. Abrams stated that while these psychedelic substances have profound brain-based effects, the evidence surrounding their use for treatment for neuropsychiatric disorders like PTSD is not sufficient, as reflected by the FDA decision. He stated that he and his organization agree with the FDA decision, highlighting the need for addressing unblinding bias, proper collection of toxicological and abuse-potential related data, and standardized therapeutic approaches. He ends by highlighting that within the sponsors studies, drug vs. non drug comparison in these trials had evidence that intensive talk therapies alone are effective in some patients in the placebo group.

Mary Armstrong, who shared their experiences with generational, sexual and physical traumas throughout her life. She described how standard forms of treatment, both therapy and medication, were unhelpful for her conditions. She shared how without Rick Doblin and MAPS, despite their flaws, she would have ended up in the bottom of a bay. She stated, “MDMA, psilocybin and ketamine…they work. Fibromyalgia will be held at bay after six doses of ketamine using the Imperial College London Method. MDMA will give you an open mind to hold your own memories in your head and reframe a lifetime of trauma. I know this as fact, because I am sitting here today.”

Dr. Neşe Devenot, researcher at Johns Hopkins University with expertise in psychedelic bioethics and well-known critic of Lykos Therapeutics. Similar to her commentary in the FDA Ad-Comm meeting, she shared her own background with complex PTSD and how she understands the need for novel medications, but that doesn’t mean the field should sacrifice safety and ethics. Dr. Devenot then when on to discuss the issues in the psychotherapy protocol in the Lykos application, “Due to the stigma associated with former underground practices descriptions of this therapy have employed euphemistic language that presented an inaccurate picture of the intervention. This has led to significant misunderstandings among researchers, which explains why the bioethics literature has not yet engaged with the highest risk applications of touch in this therapy. At its core, MDMA-AT taught that therapists can telepathically attune to their patients needs including when the patient needs to suffer for their healing. This is a scientifically discredited premise that increases the risk of boundary violations.”

Dr. Robert M. Grant, who is practicing physician and Professor of Medicine at UCSF, shared his thoughts. He also shared that he has sat on multiple FDA advisory committees for new drug applications and has researched groundbreaking research on an HIV drug that became FDA approved. He said, “I consider myself a friend of the FDA and as a friend of the FDA, it is my opinon that their recent review of MDMA failed.” Dr. Grant highlights many issues in the overall guidance provided by the FDA during the decision and how the FDA did not stand by guidance that was given to the sponsor during the application process. In addition, the FDA “failed to provide context” for their decision, specifically how the methods of blinding used in the Lykos application were not rigorous. He shared his experience as an intensive care doctor and how many of these patients likely have untreated or poorly treated PTSD, which drove him to become trained in MDMA-AT in hopes to combat the disease.

David Heldreth Jr. of Panacea Plant Sciences, a biotech company developing psychedelic medicines, provided a unique perspective regarding his work with tribal nations. He used his time to bring up generational and communal traumas of Indigenous tribes but their lack of representation in these conversations. “There are 574 recognized tribes, yet on this panel there is a variety of government agencies but there is no one from the Bureau of Indian Affairs or from the Indian Health Services. Why weren’t they invited?” Heldreth went on to provide potential ways to include these voices, such as providing more time to apply for public comments, outreach to these specific communities with limited access, and supporting these communities as much financially as veteran populations. “These things would go a long way for healing generational trauma and reducing conflict and mistrust of the government by Native communities. In that vein, many of these items being researched for PTSD actually come from Indigenous medicines, including psilocybin.” said David. “We need to honor these people and give benefits and honoring to them because this is where these medicines come from.”

Vanessa Joy Walker, representative of the Depression Bipolar Support Alliance, shared her experiences with cancer, family trauma, emotional abuse and suicidal thoughts. She shared, “Surviving survivorship is exhausting and often death feels easier than living. I had no idea that these crises and trauma could lead to PTSD, I thought that was only for war veterans and violent attack survivors. I didn’t want people to think I was broken or less than.” Walker continued to discuss in her experience, sharing that treatment is complicated and finding combinations of medication and therapy is difficult and takes time, but for some trauma survivors there is not time. She ends by highlighting the need for trauma informed care and acceleration of advancing treatments, which includes the exploration of psychedelic therapies.

Major Aaron Wolfgang, US Army psychiatrist and Assistant Professor Adjunct at Yale, shares statistics surrounding PTSD in service members and how there is a need to address PTSD to increase operational readiness. He stated, “PTSD is the most common psychiatric diagnosis for disability discharge across all branches of US military. Depending on the service, 14–27% of all disability discharged service members have service-related PTSD. The US military is currently losing thousands of service members a year to PTSD related PTSD disability discharge. Each one of these service members, is someone who may otherwise have contributed their invaluable military experience…, instead we are prematurely losing the most casualties to PTSD before the next conflict has even occurred.” He ends his comment period by sharing the need for improving the golden standards of treatment and embracing cutting edge research, which includes DOD and VA programs and clinical trials with psychedelics, as mentioned above.

Deran Young, a retired captain of US Air Force, licensed therapist and founder of Black Therapists Rock, an organization dedicated to training black therapists and heal racial trauma and other cultural burdens, shared how their organization has trained several black therapists in psychedelic-assisted therapy included MDMA-AT. Young describes how MDMA can provide a way for those with medical mistrust can seek healing of their trauma, highlighting the intersections that influence complex trauma. She ended her commentary by stating, “I believe the FDA can do a lot to change the legacy of institutional betrayal stemming for incidences such as the Tuskeegee experiments and more. We want to trust healthcare and medicine but that will only happen when voices of the people are prioritized over the stigma and politics.”

Virna Little, behavioral health clinician and national advocate, shared the Collaborative Care Model, an evidence based model to identify and treat behavioral health conditions in primary care settings. She expressed that many people go to primary care first to seek treatment, especially in areas without access to mental health resources, and therefore more clinicians should be trained to better understand mental health conditions such as PTSD. She shared that this model is in existence in 34 states, with insurance codes, and clinical trials are continuing to evidence the efficacy of these programs, thanks in part to funding by SAMSHA.

Sonja Patrick, retired veteran, shared her experience with pain treatment using hydrocodone through the VA and how sudden discontinuation following the opioid epidemic caused significant physical and mental health issues. She shared concerns that something similar may happen after psychedelic approval, where its deemed a miracle drug but all of a sudden, if problems arise, it will be taken away from those who found it helpful. “It’s great that everyone is learning, but in the end its the veterans are the ones who are suffering when you just yank it from them like that,” Patrick said. She ended by urging people doing the research and making these decisions to consider the outcome in the event that medications must be further regulated or taken out of circulation.

Conclusions

Given the sentiments shared by the panelists, public stakeholders, veterans and researchers that have been involved in this ongoing conversation, it’s obvious there is a great complexity to furthering psychedelic medicine.

While many disagreements arise from hot topics such as these, the largest take away is the need for cross-discipline collaboration to promote rigorous research and evidence-based treatments. There are so many organizations across the regulatory, industry and academic spaces that have growing interest in advancing research and medicine related to psychedelics, which is one of the reasons its so difficult to collaborate. The psychedelic field is unique in that it has individuals who are so passionate about their cause that the judgement becomes clouded, which ultimately fails the patients who need advancements in treatment.

It is important that we listen to those with PTSD, but this includes those with PTSD who have also been harmed by psychedelic therapies or by the organizations who claim to want to help those with this debiliating disorder. As mentioned and highlighted throughout this article, there are people and organizations beyond Lykos Therapeutics that want to see psychedelics through. The more these productive discussions are had, the better the outcomes for those suffering become.

Alaina was involved in the petition to the FDA to call for the Public Advisory Committee Meeting.

Background

The FDA Ad-Comm meeting convened starting at 8:30am ET on June 4th, 2024. The FDA novel drug application (NDA) for MDMA (MDMA) assisted psychotherapy for treatment of post traumatic stress disorder (PTSD) by Lykos was accepted for review in February of this year. The application was given priority status, meaning its processing will be expedited. The final decision target action date set by the FDA is August 11, 2024.

A few months after the acceptance of the NDA, no public advisory meeting was announced. In April 2024, advocates and researchers submitted a citizen petition to the FDA requesting a public advisory meeting with extended time and prioritization of stakeholders who have potential critiques on the current application methodology. The FDA had informed Lykos Therapeutics of the advisory meeting before informing the public or those undersigned and in response. The petition was altered to state:

“We are aware that the FDA informed Lykos (formerly MAPS Public Benefit Corporation) of a planned meeting in June 2024, but this meeting was not publicly announced by the time of posting this petition. This advance notice allows Lykos to organize advocates in preparation for the meeting. Although the FDA stipulates that meetings must be publicly advertised at least 15 calendar days before the meeting date, other stakeholders should also be afforded the opportunity to prepare for this meeting. Additionally, given that some former clinical trial participants are disabled, advance notice is a reasonable accommodation for their full participation in the OPH. In light of strong public interest in FDA’s decision, this meeting should also be made available by webcast.”

The FDA announced the June 4 advisory committee meeting in an official notice published on May 8, with all oral presentation requests to be filed by May 21, 2024 (an extension from the original deadline May 17, 2024). The original time slot for public comment was extended by 45 minutes to accommodate the number of oral presentations.

Representatives from Lykos presented first followed by a Q&A and break, then the FDA presented their analysis and concerns, also followed by a Q&A. The committee broke for lunch before hearing the public comments. After public commentary, the FDA panel discussed the various questions put forth:

Discuss the evidence of effectiveness for MDMA for the treatment of post-traumatic stress disorder (PTSD). Consider the following:

1. The potential impact of functional unblinding on interpretability of efficacy results
2. The durability effect
3. The role of psychological intervention in the treatment paradigm

Discuss whether the available data are adequate to characterize the safety of MDMA for the treatment of PTSD.

1. Consider the limited data collected on events deemed positive, favorable, or neutral that would inform abuse potential for this program and the lack of data from some clinical laboratory tests.
2. Comment on whether you have concerns about other safety issues and what additional data would be useful to characterize the safety of MDMA.

Discuss the potential for patient impairment to occur with MDMA and the potential for serious harm that may result due to the impairment.

Discuss whether the proposed risk mitigation is sufficient to mitigate serious harm resulting from patient impairment. Include any additional safety monitoring conditions needed for the safe administration and monitoring of MDMA if approved for PTSD.

Following this discussion they voted on two questions:

1. Do the available data show that the drug is effective in patients with posttraumatic stress disorder?
2. Do the benefits of MDMA with FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD?

In terms of the questions, there was a lot of confusion on whether the discussion and voting should take place around the drug itself, or take into account the psychotherapy component. Considering the contribution of psychotherapy has not been characterized, nor have they compared their therapy component with other types of therapy the FDA found it difficult to separate the two components. There were concerns about the 21 CFR 201.57(c)(i)(A) in which the FDA cannot regulate therapy and is only able to approve drug on its own. This alone highlights a major issue present throughout the advisory meeting.

This overview will highlight key elements from the meeting organized by topic not chronologically.

The Application

As many are probably aware, the application included three sessions of MDMA administration with psychological interventions over the course of four months. These included:

• Preparatory sessions: 3 sessions of psychotherapy to prepare and taper off any medications.
• Medication administration session with psychological support: 3 sessions with psychological support as needed
• Integrative sessions with psychological support: occur after medication sessions

There would be three medication sessions, with at least 21 days between each session. The FDA and Lykos presented different dosing regimens which is due to the formulation of the compound. The Lykos Presentation references the MDMA Hydrochloride formulation (top) and The FDA Presentation references the freebase formulation (bottom).

The Psychotherapy Component

The FDA ad-comm panel was perplexed by the inclusion of a psychotherapy component and was even told to focus on the drug-application and not the therapy component or allegations of misconduct within this component. Many sought to clarify how they should be basing their vote since the application is not just for MDMA, but MDMA-AT.

Per the Lykos briefing documents, they perform psychological intervention based on their own MDMA-assisted Psychotherapy Treatment Manual, which was developed over the years as these trials progressed. In their presentation they highlighted that the use of psychotherapy is to provide a safe environment that fosters healing without directing the patient.

It was somewhat surprising to many that Lykos representatives did not address their founder Rick Doblin’s beliefs of an “inner healing intelligence” through MDMA-AT, nor did they share with the FDA the core of their treatment manual comes from ideals from Stan Grof, a psychiatrist who is responsible for the “Basic Perinatal Matrices” and how the fetus’ experience in the birth canal predicts trauma and resilience. The concept of inner healing intelligence is widely debated and has been adapted by several underground psychedelic treatments that encourage patients to “let go” and “surrender,” which may amplify the risk of harm associated with increased openness and vulnerability from the effects of MDMA.

The Lykos briefing document shares their psychological intervention is:

• Largely non-directive; inviting inquiry and providing suggestion rather than directing the patient.
• Relied on active or engaged listening and responding and support for approaching difficult material.
• Included periods of introspection alternating with periods of communication between therapists and the patient.
• Required cultural sensitivity in support of effective, sensitive communication with patients from different cultures.

If the application is approved, Lykos plans to provide the training used in the clinical trials to therapists in post-marketing. This was something that was concerning to many of the panelists,

One panelist brought up that while the specific modalities of psychotherapy are undefined and largely non-directive, the treatment manual still follows general principles of therapeutics such as “empathy, support, fostering openness to inner experiences that may emerge, and providing a comfortable physical environment.”

During the Q&A session following the Lykos presentation, a representative explained one of the reasons they chose “psychological intervention” as a term was to allow broader uses of MDMA-AT outside of their manual. This was reassuring to some panelists, including consumer representative Kim Witczak, who was concerned that their manual would be required moving forward. Despite Lykos’ statement, they still would train the initial wave of therapists post-approval.

About 50% of the discussion surrounded the psychotherapy component, which is completely out of the FDA’s wheelhouse. A couple of committee members even asked if it was possible to consult with other experts regarding the psychotherapy component or if there was a way for the FDA to form a subcommittee to deal with these types of applications.

A significant portion of the discussion concerned therapist misconduct and how the FDA could possibly comment on this application because of the psychotherapy intervention. Many noted that the way it is presented in the application “makes it impossible to disentangle” the MDMA component from the psychotherapy component. No MDMA administration was done without psychotherapy, and with no standardized therapy it is difficult to determine how effective and safe it is for patients who are under the influence of MDMA to undergo the types of therapies present. Another major concern around the psychological intervention was that due to the fast and loose definitions given by Lykos, the therapy may differ across treatment arms and between sites, making it extremely confounding to whether or not the MDMA is what is driving these effects at primary and secondary endpoints.

What is MDMA and how does it work?

MDMA stands for 3,4-Methyl​enedioxy​methamphetamine but is called by many names and has been given many classifications. Structurally it is a substituted amphetamine with serotonergic properties, which account for some of its psychedelic-like effects including changes in perception, sensory processing and increased feelings of euphoria. It’s commonly referred to as an empathogen or entactogen due to its ability to increase feelings of empathy towards oneself or others, which is one reason for its use as an adjunct to psychotherapy. Onset of subjective effects following oral administration of MDMA typically begins within 30 to 60 minutes and reaches peak effect at 75 to 120 minutes, which then plateaus for about 3.5 hours. MDMA is a commonly used recreational drug in the music scene with some abuse potential, due to it causing physical dependence in some individuals and withdrawal symptoms if frequent use is suddenly stopped.

The main way MDMA alters signaling in the brain is through its effects on monoamine release. Monoamines are neurotransmitters such as dopamine and serotonin, for example, which are released from specific neuron populations in various brain regions. MDMA enters these neurons through monoamine transporters, and has high affinity for transporters of dopamine, norepinephrine and serotonin.

The methylenedioxy- substitution provides the serotonergic activity, as most other substituted amphetamines show negligible affinity for the serotonin transporter.

It is important to note that MDMA has two structural isomers called enantiomers: S)-MDMA and (R)-MDMA. Typically the racemic mixture of both isomers is used recreationally, but through pharmacological research it’s been evidenced that (S)-MDMA causes the entactogenic effects through its affinity for the transporters, whereas (R)-MDMA has notable agonism towards 5-HT2AR which is thought to contribute to the mild psychedelic-like effects induced by high doses of MDMA. Lykos’ studies used racemic MDMA which contains both enantiomers.

As for the way MDMA works in the context of PTSD and psychotherapy, the research is still ongoing. Lykos’ presentation included a slide that highlights how MDMA assists psychotherapy which included:

• May increase patients sense of empathy and connectedness
• May foster patient’s sense of safety and trust
• May increase recall of affectively charged memories
• Serotonergic effects of MDMA often translate to transiently reduced anxiety

While MDMA has been evidenced to foster a sense of empathy and trust, and/or reduce anxiety in some patients, some patients may respond differently. MDMA administration can also put patients in a vulnerable or susceptible state. Further, the effects of MDMA on memory is still a highly debated field with some studies showing the opposite of Lykos’ claims (Bershad et al., 2016; Kuypers and Ramaekers 2005; Doss et al., 2018).

In one of the highlighted studies, Doss and colleagues found MDMA given at either the encoding or retrieval phase did not affect overall memory accuracy, but when given at the encoding phase, “MDMA reduced recollection estimates for negative and positive pictures but had little to no effect on neutral items or familiarity estimates.” It’s not to be remiss that there is evidence for MDMA to positively affect memory recall (Carhart-Harris et al. 2014; Ballard et al., 2014), but it’s important to remember these studies are still ongoing.

Despite this, the idea is that MDMA administered with psychological support will allow patients to revisit their trauma without negative feelings and in a more open state of mind. It’s important to note these experiences are often difficult, emotional and overwhelming. Despite this, many participants completed the MAPP1 and MAPP2 trials with positive results as shown by Lykos’ presentation and in their briefing documents.

The Data (Lykos and FDA Presentations)

The primary endpoint for both MAPP1 and MAPP2 was a change from baseline to week 18 in the clinician administered PTSD scale (CAPS-5), specifically 10-point or greater change in treatment arms was considered clinically meaningful. The CAPS-5 is based on DSM-5 criteria and is the industry standard for PTSD trials. The secondary endpoint was a change from baseline to week 18 on clinician-rated functional impairment using the Sheehan Disability Scale or SDS across domains.

The only differences between MAPP1 and MAPP2 that was highlighted was that MAPP1 included participants with severe PTSD, whereas MAPP2 included participants with moderate to severe PTSD, and MAPP2 incorporated an unblinding survey.

Both studies had a clinically meaningful and statistically significant difference in reduction of CAPS-5 at week 18 after MDMA sessions.

• Approximately a -24-point mean change in MDMA arm
• Mean change in both MDMA and placebo arms were clinically meaningful
• Difference between MDMA and plaebo arms was approximately 12 points

Both studies had a clinically meaningful and statistically significant difference in reductions of SDS disability scale at week 18 after MDMA sessions.

• Approximately a -3-point mean change in MDMA arm
• Mean change in both arms was considered clinically meaningful
• Difference between MDMA and placebo arms was approximately 1.3 points

The unblinding data for MAPP2 revealed that study participants were able to guess their treatment with a high degree of accuracy, more so in the MDMA arm, which is unsurprising given the strong subjective effects with MDMA and other psychedelic-related compounds. This was a large problem for the FDA but there was little solution offered and no computational approaches to account for unblinding.

In attempts to mitigate this blinding issue, efficacy assessments were conducted by a pool of mental health professionals with graduate-level training in psychology, social work, or counseling and at least 1 year of experience working with a trauma-exposed population. Reviewers were blinded to study design, assessment timepoint (except baseline), and safety data collected by sites, and no reviewer was to assess the same patient more than once. These folks were not onsite and conducted assessments over live video conferences.

In addition to adding the independent reviews, Lykos also tried a string of studies to use low doses of MDMA, but ultimately decided these doses worsened patients, although sample sizes were relatively small.

An exploratory observational study, MPLONG, was also included to explore the durability of treatment effect after 6 months in participants who chose to enroll after completing the parent study. Data from this study suggest that MDMA effects on PTSD symptom severity persist after 6 months and up to two years in some patients.

The FDA noted caveats in MPLONG, which included:

• On average, participants who enrolled for MPLONG had less severe PTSD symptoms compared to those who did not enroll.
• MAPP1 participants who enrolled were already formally unblinded to treatment
• Time for long-term follow-up varied considerably among participants, some from MAPP1 were up to two years post-completion.
• Interim drug use of psychedelic-related compounds between parent study and MPLONG
• Including MDMA, ketamine and 5-MeO-DMT
• Unsure about other compounds

To attempt to get at some of these issues, the FDA did its own exploratory analysis, treating any data collected after interim use of non-study drug considered as missing. The purpose of this is to determine if other drugs impacted prolonged durability of MDMA’s efficacy. They found that removing data varied by parent study and arm. In MAPP2, results were less favorable in the MDMA arm but better in the placebo arm. In MAPP1, results varied depending on the analysis methodology for the MDMA arm, but remained stable in the placebo arm.

Safety (Lykos and FDA Presentations)

The overall safety profile observed in the program aligned closely with what has been previously described about safety issues associated with MDMA in the literature. The drug was well-tolerated with mostly transient mild to moderate adverse events (AE). Only one patient discontinued due to an AE.

Most common AEs occurring in at least 15% of patients were within expectation and consistent with the known mechanism of actions for MDMA (see below):

One large flaw the FDA noted was the lack of AEs collected if the sponsor deemed them to be “positive, favorable or neutral,” which includes several subjective effects. As shown in the timeline, the FDA provided clear guidelines for collecting AE data in 2017 and voiced concerns of AE and safety data again in 2022.

The sponsor stated in their presentation that:

“Acute [subjective] effects are thought to be a central component of long-term treatment benefit, and this altered mental state may result in patient impairment as an effect of MDMA… as noted in the briefing document we did not collect positive or neutral [subjective] effects of treatment in our trials as we interpreted adverse to be negative.” They also noted they are prepared to collect this data in a post-approval context to further the safety profile of MDMA-AT.

Suicidal ideation (SI) and behavior was another large concern, especially in this patient population. Only a small number of severe adverse events (SAE) were reported related to SI/behavior and only occurred in the placebo arm in MAPP1. Of these cases, one participant dropped out of the study and another remained in the study following suicide attempts until day 132 of the treatment. No SI related SAEs were reported in MAPP2, as reflected by the FDA and Lykos briefing documents.. AEs related to SI that were assessed as mild or moderate were around 40% for both arms, with no immediate behaviors post-drug administration. Other psychiatric symptoms were consistent with PTSD itself, or can be related to serotonergic or stimulant properties.

It’s important to note that issue has been raised with Lykos’ inclusion of suicide-related SAEs in the final dataset, as well as them dissuading people from participating in the follow-up study if they had worsening symptoms or did not respond to MDMA treatment. The FDA stated that these, along with other allegations of misconduct and criminal behavior across the clinical trials including sexual assault, are being investigated by the agency.

Further safety assessments on blood pressure and cardiac events were presented, as they were noted to be AESIs due to MDMA’s effects on heart rate. Patients with moderate cardiovascular risk underwent additional screening measures, including stress testing. Patients were excluded if they had relevant conditions such as uncontrolled hypertension, significant cardiovascular or cerebrovascular disease, and/or atrial and ventricular tachyarrhythmias. All vital signs measured pre-dose, interim, and at the end of medication sessions. When the agency asked why blood pressure and heart rate were not measured throughout the study the sponsor said that equipment and consistent monitoring would’ve interfered with the MDMA-AT process by being intrusive.

Some other questions for the Lykos team included:

• How participants were recruited and whether recruitment through referral or certain internet forums “stacked the deck” for people with experience with MDMA and other psychedelics. Specifically noting that 40% of participants had prior MDMA experience.
• Lykos responded by showing data that evidenced there was no difference between primary outcomes for those who had an MDMA experience and those who did not
• How interim therapy before the follow-up influenced MPLONG results.
• Over 70% of patients in either arm had received any psychotherapy in between the parent study and MPLONG, with the majority being in the undefined category
• Several in the placebo group had a form of cognitive behavioral therapy, EMDR and psychodynamic therapy which are commonly used for PTSD treatment
• How could concomitant medication potentially confound results?
• Approximately 90% of both treatment arms reported concurrent use of at least one medication
• 20% of patients in the MDMA-arm were using psychostimulants for ADHD and nootropics, which given their similarity in pharmacological profile or physiological properties to MDMA, could be confounding.
• How would the therapist team look in post-approval, whether relationships between therapists should be assessed including financial or mentorship relationships that may compromise ability or willingness to intervene.
• Lykos CSO stated that guardrails should be considered when developing the post-approval therapy team
• How would MDMA be kept from diversion outside of its approved indication?
• Lykos noted that they would begin with a limited roll out that was only available in specific healthcare settings, mandatory enrollment in a registry monitoring the drug, and use single-dose packaging.

Proposed REMS (Lykos and FDA Presentations)

A large discussion focused on proposed Risk Evaluation and Mitigation Strategies (REMS). The FDA stated,

“REMS must be determined due to potential for harm associated with impairment after exposure to MDMA,” but they are not sure what these REMS would be at this time given the lack of AE and other safety data. A large issue noted by the panel was the lack of laboratory assessments post-MDMA, which is included in every NDA application, but due to some poor oversight the reviewer for the agency did not notice this data was missing. One of the committee members stated: “both the applicant and we have to take responsibility…”.

Ignoring this huge issue (which is apparently what the agency and Lykos did), REMS were proposed by both groups. The Lykos proposed REMS was limited and focused on supporting safe use through patient monitoring and provider training as they do a limited roll-out.

The FDA spent a lot more time focusing on proposed REMS, of which some of the suggestions overlapped with those proposed by Lykos. They noted the following:

The drug be dispensed only in certain healthcare settings, which include:

• A prescriber is available during midomafetamine administration and monitoring
• At least two healthcare providers are onsite (one of which must be a licensed healthcare provider) to monitor the patient’s medical (including vital signs) and psychological status for at least eight hours or until the patient is stable to be discharged
• Emergency action plans are in place to escalate care if needed based on the patient’s medical or psychological status
• Plans are in place in case the patient requires longer monitoring
• The patient is stable to be discharged from the healthcare setting
• The patient is released to an accompanying adult after each medication session

The drug must be dispensed to patients with documentation of safe-use conditions and patients must enroll in REMS, which include education on:

• Potential effects and risks of midomafetamine
• Need to be monitored for at least eight hours
• Need to leave the medication session with an accompanying adult
• Not to drive or operate machinery until at least the next day
• Need to follow up with the healthcare setting after medication sessions
• Each patient using the drug be subject to monitoring
• Each patient using the drug be enrolled in a registry, of which data collected will include but not be limited to:
• Signs and symptoms of mental or physical distress experienced by the patient
• Onset and duration of short-term effects
• Monitoring duration
• If care needed to be escalated
• Safety after medication sessions including the occurrence of events indicative of serious harm from patient impairment from midomafetamine administration
• Implementation system to assist with operationalization of the REMS
• Timetable for submission of assessments

FDA also noted other issues that need to be addressed separate from REMS, which included:

• Return of blood pressure and heart rate to safe level prior to discharge
• Addressing risk of adverse cardiovascular sequelae in patients with preexisting cardiac disease
• Focus on mitigating events resulting in hospitalization or death, events that could put someone in the hospital or death (driving, walking into traffic, etc.)
• Negative consequences like sexual assault or financial coercion
• Worsening psychological disorders that cause disability
• Suicidal ideation and behavior

Most importantly, the panel stated many times throughout the meeting that proper REMS could not fully be determined at this time due to a lack of safety data surrounding cardiac events, AEs, and laboratory assessments.

Public Commentary

This was perhaps the most awaited part of the ad-comm meeting, given they had to extend time to accommodate all the speakers. There were 32 oral presentations, approximately 20 that were in full support of the application, 10 that were against the application but in support of MDMA-AT as a concept, and 2 that were neutral. One oral presenter was not present, bringing the original count of 33 down to 32. Each speaker had 3 minutes and were promptly cut off if they went over. While I will not be recounting every comment, I will highlight some that moved me.

If you are interested in reading the written comments, please check out that coverage from my colleagues at Psychedelic Alpha: Patients, Practitioners, Researchers and Public Submit Comments Ahead of FDA Advisory Committee on MDMA, May 29.)

Russell Hausfeld, an investigative journalist and writer at Psymposia, shared his research and reporting from the last eight years on the developments of Lykos Therapeutics. He noted when he began covering this topic and organization, he had aligned with “the goals to legalize and destigmatize psychedelics,” but after years of reporting felt “it would be irresponsible to endorse this company…” After discussing some of the misconduct he had heard through his reporting, he highlighted the words of some of the veterans who volunteered their stories of mistreatment in 2022. Hausfeld quoted one such story,

“I [the veteran] watched as they used veterans and discarded them as soon as they no longer served the useful purpose, regardless of mental health consequences or social implications.” Another veteran quote included, “If this treatment by Lykos is happening to me, it concerns me about the population that Lykos will be working with moving forward.”

Jonathan Alpert, Chair of the Council On Research for the American Psychiatric Association, shared his thoughts on the efficacy of the trials. He stated that while decreasing symptom ratings represent promising treatment for a devastating illness, there are significant limitations to the current evidence based on MDMA for PTSD. He highlighted bias and functional unblinding of participants, as well as the participants in the phase 3 trials prior exposure to MDMA.

“ [prior use] …is unusual for drug treatment studies. That means that people who presumably had positive or neutral effects from MDMA in the past might be more likely to have participated…,”

highlighting the threat to the generalizability of the studies. He concluded by noting the APA supports research and therapeutic discovery of psychedelic agents that are pursued with the same scientific integrity, rigger and regulatory standards applied to other promising therapy. This includes future research with head-to-head comparison with other FDA approved medication.

Kayla Greenstein, a psychology candidate at the University of Sydney with experience in sexual assault response shared her thoughts despite it being 4am her time. She shared how she wanted to conduct a psychedelic clinical trial for PTSD, but as she looked at the psychotherapy component, she quickly realized there were serious issues in the research protocol.

“I read the therapeutic manual very closely, and I’ve read all of the references in the manual,” Greenstein said. “The core of the therapy is that we all have an inner healing intelligence that can be accessed through MDMA and other non-ordinary states of consciousness. Given the centrality of the inner healing intelligence in their therapy manual and mechanism of action, I was really surprised we didn’t hear more about it today from the sponsor.”

She further shared that through her research she discovered the manual is rooted in ideas that trauma originates in the birth canal, which includes homosexuality. She urges, “this is not a safe therapy model,” highlighting the lack of recognition of the role of coercive control and increased vulnerability.

She ends by saying, “I am still hopeful about MDMA therapy and I look forward to seeing the research from labs that are not associated with Lykos. I wish I could support this application however, I believe approving this model of MDMA therapy would result in substantial further harm.”

In the same vein, Dr. Neşe Devenot, researcher at Johns Hopkins University with expertise in psychedelic bioethics, shared their concerns with the Lykos protocol. They open by stating, “This committee has been misled by Lykos to believe this intervention was nondirective and empathetic.” Devenot continued,

“The therapeutic approach is based on spiritual teaching, and the essence of that treatment approach is a death-rebirth process. Although this specific intervention isn’t in any of the briefing documents that were submitted to the committee, it is associated with identifiable patterns of harm across like clinical trials.”

They then went on to highlight an excerpt from Integral Psychedelic Therapy, where Lykos supervisor and therapist, Veronika Gold, touted consent violations and use of physical force as a part of the therapeutic process, dismissing the distress of her patient. Devenot urges the agency to take her comments into consideration and think about what other instances of misconduct Lykos is not sharing.

Ifetayo Harvey, Executive Director of the People of Color Psychedelic Collective, began her comment by sharing that she had previously worked as an assistant at the Multidisciplinary Association for Psychedelic Studies (Lykos previously was MAPS Public Benefit Corporation) for eight months in 2015. “Despite my poor treatment as an employee,” Harvey said. “I am grateful to MAPS for starting a movement around psychedelic healing in clinical settings.” She went on to state, “this is the first time, in my opinion, that advocates have had the space to share and have others engage with our concerns. There’s a tendency in the psychedelic community to shy away from critiques or confrontations.” Her main critique was that the field and MAPS regularly dismiss valid concerns from other critics and refuse to engage. There needs to be an effort to improve and ensure consumer safety, especially after seeing the evidence of abuse, crossing of boundaries and discrepancies in data. Harvey states,

“I’ve concluded that there needs to be more rigorous research on MDMA psychotherapy before it’s brought to the public.”

MDMA researcher and CEO of Tactogen, Matthew Baggott, sought to provide comment on risks associated with the application. Importantly, he highlights NIDA has funded 460 million dollars of projects involving MDMA. In which, over 1,500 participants have been given MDMA in studies not sponsored by Lykos. Baggott says, “controlled MDMA-administration studies document manageable physiological risks such as time-limited cardiovascular changes and, when fluid intake is unrestricted, hyponatremia.” He also spoke on potential harms related to vulnerability. “Controlled MDMA-administration studies also confirm acute self-report changes in mood and social feelings. These changes, combined with MDMA’s history, raise reasonable concerns that MDMA might increase patient vulnerability to boundary violations or other harms.” Ultimately, and despite being CEO of a company that is a direct competitor with Lykos, Baggot states

“It is clear that MDMA can be used with acceptable safety under medical supervision. Additional data will help quantify likelihoods and time courses of specific risks in patients, but the balance of apparent benefits and risks appears to be favorable.”

Veteran organizations such as the Wounded Warrior Project, Veterans of Foreign Wars and Disabled American Veterans spoke on behalf of their members, pointing out the large need for novel treatments for veterans with PTSD. Many highlighted the overwhelming statistics of veteran suicide and comorbid disorders. Several participants, of which many were veterans, provided public comments with extremely positive things to say about their participation in the clinical trials, some of which I will quote below (and regret that my AI voice-to-text did not capture the names of the speakers):

“…I couldn’t imagine a world where there was a solution, now I get to fully live my life. My perspective on the world has changed because my perspective of my experience changed…I learned that I was living in survival mode, and once I was able to process my grief and trauma I felt self-empathy and self-love for the first time in decades and my trust in this world grew again. I started looking at the glass full instead of being stuck in this endless victim narrative.”

“…I kept searching for new treatments and found this trial. Within the very first hour of the MDMA session. I felt an intense sense of repair and spontaneous rewiring of my body. The effects were immediate, the emotional flooding banished what used to feel like a tsunami of overwhelming panic to now merely a puddle at my feet. A change of perspective is everything and MDMA is a reset button… This was hard work, but the results were life-changing. None of my previous therapies came close to unraveling all of my trauma. The best aspect of this medicine is that I no longer need it. My MDMA training wheels are off and I remain resilient after those three sessions.”

“I was very fortunate to be accepted into a trial after reading about social media and applying. I was entering the trial with a healthy dose of skepticism, having numerous treatments in the past without success and hearing about this treatment…These sessions became a pathway to explore a new outlook through this love and appreciation, transforming my relationship with others. But, also, I wouldn’t claim that MDMA eradicated my PTSD upon completing the trial…but also, I no longer have the symptoms that tormented me for years. I am experiencing a newfound ease and laughter, and a profound sense of lightness and calmness…This transformation has made me a more effective partner, parent and most significant to me, is granting me the enjoyment of motherhood.”

“I’ve lost count of all the people who reached out to me to say ‘I was going to kill myself, but I saw you so I’m going to wait…’ For the last decade, I had to tell hundreds of people who have reached out to me that help is coming, but we have to wait for the proper approval process… I fear what will happen to them if this therapy is not approved.”

Despite the many raves for MDMA-AT, some people shared negative experiences. Beau Witka described a guided therapy session from someone who received training from the California Institute of Integral Studies — which provides training for Lykos studies — that made his PTSD worse. He shared that following this experience he experienced symptoms that completely “derailed his life” which include “extreme exhaustion, brain fog, and severe cognitive impairment.” He also shared that he had a positive experience after, which is helping him recover from the devastating first guided experience. He fully supports MDMA-AT as an option, but cannot support MDMA therapy being available to the mainstream without additional focus on training and helping those with extended difficulties.

In one of the most moving presentations, was a statement read on behalf of trial participant Meaghan Buisson, who was specifically recruited to the study by Lykos. The letter stated that the trial sponsor failed to consent the day before her first session and they found something in her screening, which qualified her for exclusion criteria and was ignored to keep her in the study. Her letter reads in regards to the harms suffered in the trial,

“I will not be going into detail. There is a video available online. The fact that it and my name are public is extremely difficult. It should never have been necessary.” Buisson shares that she now suffers new symptoms of PTSD, including a distrust of medical providers, and urges “the panel to reconsider the veracity of Lykos’ claims.”

Misconduct Concerns

To many peoples’ surprise Lykos did mention the case of misconduct that took place in the Phase 2 Clinical trial, which resulted in some changes to their protocol and an internal investigation. Despite their attempts to circumvent this discussion by mentioning it in their presentation, this was something that was discussed throughout the 9 hour long advisory meeting. Information on this specific issue can be found here and here.

In the Q&A portion following Lykos’s presentation, patient representative, sociologist and qualitative research consultant at the Injury Prevention Research at University of North Carolina Chapel Hill, Elizabeth Joniak-Grant, said “let’s try not to gloss over this misconduct; it was sexual misconduct”. This is especially important when discussing treatment for PTSD, where several folks have sexual violence related traumas. Joniak-Grant later voiced several points on the lack of data and inability of Lykos to provide more information before the voting. These included concerns over misconduct and the ongoing investigations, stating “I can’t in good conscience support something where these many harms are being reported.”

Another panelist referenced the misconduct and ‘probably criminal violations’ in his question about therapists and relationships, asking Lykos how that would be addressed moving forward. Their response that there should be consideration on this topic. In the discussion prior to voting, this same panelist again raised some serious questions about the sponsor being able to educate and deliver psychological intervention in a responsible way.

“Unfortunately there has been misconduct that has occurred, which really polluted our ability to interpret the data.”

Consumer representative, Kim Witczak, brought up the misconduct from a different perspective. They noted that while they are pleased to see this treatment as something that is being discussed today, they are concerned with the misconduct allegations. “Usually this happens when something is on the market already,” highlighting that this typically comes with lawsuits, pricey litigation, and public concern. “We have an advantage to investigate before that.”

Summary of Discussion and Major Review Issues

“We are creating a new field of medicine…and we don’t take this lightly.”

“Amidst the complication of all of this, the patients deserve the opportunity for us to move forward and this regulated way is the only way to do this.”

These are just a few of the statements before the discussion and review after all the presentations. Below I will highlight the major points discussed by the panel as it relates to each question and their final votes.

Question 1. Discuss the evidence of effectiveness for MDMA for the treatment of post-traumatic stress disorder (PTSD).

Major Issues:

• Functional unblinding degrades confidence in efficacy
• Only attempt for comparator was smaller doses MDMA, rejected other suggestions
• Blinding not tested in MAPP1
• Unblinding of therapists during sessions
• Expectancy bias within sample
• Issues with recruitment and recruitment methods
• Confounding variables in the long-term durability data
• Unblinding of MAPP1 before follow-up
• Length of follow up differs between participants
• Confounding substance use and intermittent therapy
• Generalizability
• Prior exposure to MDMA vs prior exposure to standardized therapy
• Lack of diversity in race/ethnicity
• Lack of diversity in PTSD severity
• Disentangling of the psychotherapy component and MDMA treatment
• No non-therapy arm or drug-only arm, lacking 2 x 2 design to determine MDMA effectiveness of the drug alone
• No standardized therapy approach across arms and sites

One of the panelists stated the results are “really promising and it’s obvious this treatment has impacted a number of people in positive ways, but there are problems with the data.” She continued by pointing out, “One or two [data issues] may be okay and addressable, but when you pile them on top of each other there isn’t enough convincing evidence.”

One comment was quite interesting, as it caught on to the uniqueness of the psychedelic field and this application. ‘The language use is unlike most things that we see,” They said, highlighting several public commenters referring to these studies as being part of a larger “movement”. The panelist points out this so-called movement has a large following which could influence expectancy and explain why there is such high background use of MDMA and low drop-out rates. They further state these points all may be “suggestive of a high level of interest in engagement and allegiance.”

Question 2. Discuss whether the available data are adequate to characterize the safety of MDMA for the treatment of PTSD.

Major Issues:

• Missing data
• Lack of collection of laboratory assessments (which the FDA admitted is the fault of both parties)
• Hepatotoxicity, hyponatremia, drug-drug interaction data
• Safe medication titration data
• Lack of AEs collected despite FDA asking specifically for them
• AEs that sponsor deemed positive, favorable or neutral
• Concerns over omissions of other data that they didn’t consider AEs (i.e. distress)
• Specifics on Dropouts and withdrawn consent
• Never received information from Lykos

One panelist noted that while they are less concerned with things like euphoria and blissfulness as it relates to “abuse potential,” they are more concerned about how these positive feelings may “make it easier for clinicians to prey on vulnerable patients.”

Despite missing data a few panelists including Walter Dunn, were confident that many of these could be addressed post-approval. Some panelists noted that phase 4 trials would be necessary to assess some of the potentially safety concerns, specifically with cardiac events. Phase 4 trials are typically to assess side effects that are not seen in earlier trials and can also be used to assess how well a novel treatment is working in the general population over a long period of time.

Others were not so convinced. While excited about the potential of MDMA-AT, one panelist stated:

“We’re building the airplane as we’re flying it, and while that’s ok with something like blinding, that is not okay with safety concerns.”

Another commented on the fact that there are already evidence based treatments, of which many of the participants did not attempt before the trials. While these other treatments have dropout rates, the panelist pointed out they have strong outcomes and take around 12 h of therapy, whereas the Lykos treatment has 40+ hours of treatment and potential lifestyle changes that put a burden on access for patients and on the providers.

This discussion took a turn to discuss diversion of MDMA from its indicated use, and was spearheaded by the Committee Chair, Rajesh Narendran. He voiced several concerns that “illicit MDA is going to soar.” He further went on to say, “I would not be surprised if people go home and use cocaine, you know, use alcohol I mean with their partner who is supposed to be responsible, you’re going to have left and right issues, that’s my personal feelings on it.” Many people watching were confused by this rant, especially since diversion would be addressed in REMS and through the Drug Enforcement Agency.

*As a pharmacologist, substance use researcher and psychedelic researcher I have to comment that these personal insights by Narendran were not based on evidence or fact. The present application does not have anything to do with cocaine or alcohol use and the data presented to him do not suggest any use of these substances after sessions. This attitude is wholly inappropriate and further stigmatizes drug use, especially in vulnerable populations like those with PTSD.*

Question 3. Discuss the potential for patient impairment to occur with MDMA and the potential for serious harm that may result due to the impairment.

Major Issues:

• Staffing Needs and avoidance of power dynamics
• Trainees should not be used as core staff
• Two licensed therapists of similar standing should be present
• Need for ancillary staff like nurses and technicians to mitigate potential emergencies (attempts to harm self or others, elopement)
• Titration off other medications like SSRIs
• Lack of data on titration and potential withdrawal from medications before and during study influencing drug effects
• Discharge Guidelines
• Adult should have to accompany the patient home
• Overnight stays might be necessary

For the third question, the panel was advised by an FDA Representative that the discussion and voting should be based on what was contained in the briefing documents and open public hearing not “unfounded complaints of misconduct.”

Some panelists were concerned over the lack of diversity in the trials and how that might cause issues in a general roll-out, stating that cultural differences may influence response to the drug. Others rebutted, suggesting that diversity only is an issue in drug approval if there is a physiological reason for the drug to produce different results due to race/ethnicity/sex/gender.

Question 4. Discuss whether the proposed risk mitigation is sufficient to mitigate serious harm resulting from patient impairment. Include any additional safety monitoring conditions needed for the safe administration and monitoring of MDMA if approved for PTSD.

Major Issues:

• Not enough information to inform REMS properly
• Lack of safety data including characterization of subjective effects
• Necessity for labs to be done before, during and after treatment
• Outside accreditation and training for personnel
• Including medical training to respond to physiological events
• Training and accreditation outside of Lykos Therapy Manual
• A way to ensure safety of patients from misconduct
• Registry and independent entity to report AEs
• Potential surveillance with explicit direction about review

Surveillance was a large topic in this discussion question. Many noted that having surveillance may be beneficial to review sessions and ensure patient safety, but others noted that many PTSD patients may not consent to surveillance due to issues with trusting others, including healthcare professionals. One panelist said, “surveillance rarely ever gets looked at” and there needs to be “very explicit directions in terms of what we are going to do with that surveilled information.”

The Vote & Final Thoughts

1. Do the available data show that the drug is effective in patients with posttraumatic stress disorder?

2 YES // 9 NO

1. Do the benefits of midomafetamine with FDA’s proposed risk evaluation and mitigation strategy (REMS) outweigh its risks for the treatment of patients with PTSD?

1 YES // 10 NO

Many committee members note the decision was difficult given the promise of data and significant p-values, but were overall concerned with recruitment, durability and unblinding ultimately led them to vote no. Many echoed the same sentiments,

“too many missing parameters”

“we’re still trying to understand the risks’’

“its new territory”

For the one person who voted yes to both, Dunn explained why.

“REMs are still in conversation between sponsor and agency, but I think it’s 75% of the way there and small tweaks would be fine to address these…I ultimately voted yes because we are in dire need of new treatments for PTSD… and this has potential to make a difference.”

Although this is an advisory committee, the FDA does not officially decide on approval of Lykos’ application for MDMA-AT for PTSD until August 11, 2024. In the meantime, they may do more data analysis or come up with REMS that both parties agree to. It is unclear whether the investigation of the FDA into the misconduct and data omission claims will be complete before August 11 and whether or not this investigation will prevent approval.

Update as of 9/6/24: FDA decided to reject Lykos NDA for MDMA-AT to treat PTSD highlighting the need for more rigorous phase 3 clinical trials.

A recent article titled The Psychedelic Evangelist from the NY Times dropped a few months ago, which inadvertently reignited a fire within me. This article, among many other recent thoughts, inspired me to write up my second installment of “The Psychedelic Renaissance: What is Going On?”

If you missed the NY Times piece I’m referring to, it largely discusses the potential issues surrounding increased emphasis on religion, spirituality and mystical experiences within the studies done at Johns Hopkins University. It points out the set and setting of these offices and clinical trial sites, noting that they contain some interesting components. For example:

“…the laboratory looked like a living room, with a couch, a selection of spiritual and art books and a shelf holding a Buddha statue.”

“…delivered the psilocybin pill or a placebo to participants in a chalice-shaped incense burner from Mexico…”

These unique artifacts and some anecdotes from others, have brought criticism to these trials suggesting that there is a hyper-religious influence in these trials that is causing bias within the mystical experience results. While these issues can be discussed at length, I think one thing remains clear: more transparency about the ongoing studies is necessary. If someone wants to study religion/spirituality/mystical experiences there is no issue with doing that using set and setting, but don’t claim your study is investigating a different primary endpoint or outcome.

The Psychedelic Renaissance

This movement of psychedelics being called The Psychedelic Renaissance is quite on the nose if you think about it. Renaissance comes from the French word meaning rebirth, and this period in history was a period of cultural change, more specifically the transition from the Middle Ages to modernity. What is interesting about the original renaissance is that it focused largely on humanism, with one of the core characteristics being the increased use of observational learning, reasoning and empirical evidence. Further, one of the purposes of humanism was to create a universal man — aka the renaissance man — whose combined intellectual and physical excellence would make them the most prototypic human being.

So fast forward to now to The Psychedelic Renaissance where it seems the humanitarian reasoning and concept of rebirth is alive and well (and maybe some of the hyper fixation of ancient Greece and Rome), we are now moving into dangerous territory where the new renaissance man is someone who is spiritually enlightened by psychedelic-assisted therapy. Where if you kill off your ego, you will have this perfect storm of intellect and emotional excellence to get you through the rest of your life. Some believe this will be attained in part through action involving the inner healing intelligence, where “surrendering” to the inner healer is the therapeutic aspect. This concept has yet to be empirically tested or evidenced, but yet many in the psychedelic field subscribe to this type of thinking. Can the inner healer be tested in western medical models? Is this concept hyper-spiritual or religious, and if so, should it be allowed in a clinical trial?

Instead of The Psychedelic Renaissance, I find it better to call it The Second Wave of Psychedelic Research. And unfortunately, not dissimilar to other second wave movements like second wave feminism, this psychedelic wave has been largely led by white folks in high places with enchanting personalities, a thick rolodex, and lined pockets. And while maybe they had good intentions from the beginning, wanting to understand these powerful mind-altering drugs and support a rebirth, this shifted to the healing of the masses rhetoric, and now we see large focuses on being one-stop shop curatives, ways to improve energy and performance, and optimizing your mind to better serve capitalism. The problem? All of this ongoing research is aimed at one thing: fix the individual. This individualistic mindset of western medicine that the problem is within a single individual, takes away from the overall needs of the collective.

If psychedelic research is only focusing on the question of the individual and only allowing these well-off white men to define specific medical paradigms, then how are we as a field supposed to move forward in understanding things outside of that medical framework? The deeper I get into the field, the more I realize psychedelics don’t fit here exclusively.

I want to highlight that empirical evidence is important (hello, I have a PhD), but how can we utilize a system that wasn’t made to measure these profound experiences — or lack thereof in some cases. Can’t there be a way for spiritual and medical inquiry within the psychedelics field? Why are we so focused on favoring one over the other? This system is clearly not working for this second wave. We cannot function within a broken system and psychedelics are not proving to fix this broken system. This is obvious from the NYT article.

What else is obvious? That there is a blatant lack of involvement of Indigenous experts in the mainstream psychedelic field. Who is being consulted when these studies are being designed? Who is having discussions about how to measure the hard-to-measure like spiritual outcomes associated with psychedelics? Who is working towards the healing of the individual or and who is working towards the healing of the collective?

Ceremonial Hijacking

All of this conversation around the NYT piece has led me back to something I talked about in Part 1 of this thought-piece, ceremonial hijacking. This refers to the co-opting of Indigenous knowledge, ceremony, and tradition for personal or professional gain that does not have any benefit or collaboration with the groups from which these traditions are derived. Basically, cultural appropriation in psychedelic research which is not new.

The reason I came back to this concept is because let’s face it…psychedelics have been westernized. Within this second wave, as I mentioned above, these western medical models tend to ignore things that cannot be empirically quantified including profound mystical or spiritual experiences. What is quite interesting to me is that medicalization/westernization is such a large critique of the psychedelic field overall, but when Hopkins attempts to preserve some sort of tradition and ceremony within their studies, they are hounded for being too spiritual. So what is the middle ground, if any? Or is there a different underlying issue in this new age psychedelic spiritualism?

I think something stinks. One commenter of the NYT article put it, “This article smacks very hard of epistemological imperialism.”

While everyone is busy arguing over the internal drama of Hopkins and what is the correct way to study psychedelics, I’m left wondering: where is the critique of how some of these attempts to “preserve the ceremonial ritual” are really just appropriating specific pieces from Indigenous traditions that researchers find intriguing, giving these studies a performative aspect that make everyone feel better about co-opting Indigenous culture?

If these studies want to investigate aspects of ceremonial use, religion and spirituality surrounding psychedelics, why aren’t they including Indigenous Peoples in their study design or on their grant applications?

Benefit-to-Risk

It’s not just about inclusion. It’s about benefits coming back to the communities, protection of intellectual property, preservation of tradition and sacred medicines. In an article titled Ethical principles of traditional Indigenous medicine to guide western psychedelic research and practice, Dr. Yuria Celidwen and colleagues discuss many concerns including consent, protections and more.

In case you were like me and weren’t aware, there is something called the Free, prior, and informed consent (FPIC) is a specific right that pertains to Indigenous Peoples under the United Nations Declaration on the Rights of Indigenous Peoples. According to the FPIC, before an action can take place that would affect Indigenous Peoples, positively or negatively, the person or community must give approval for the activity to move forward. Consent must be based on the full information regarding the activity, before the activity begins and without pressure or coercion; otherwise, the consent is meaningless.

Unfortunately, FPIC has not been historically honored or understood in the context of western medicine. For example, the Havasupai Tribe in Arizona gave blood to researchers for what they thought was diabetes research, but instead the University of Arizona gave samples to others for DNA research unrelated to the original research outlined in the informed consent. This betrayal and several others have disproportionately affected black and brown communities for decades, and yet folks still wonder why clinical trials have a hard time recruiting non-white individuals.

In addition to issues with policy covering consent of Indigenous Peoples, there is currently no policy that has been designed to address Indigenous traditional medicine’s commercialization within the western medicine world. There are attempts at protections of intellectual property that vary by country, but despite many efforts to protect various Indigenous manifestations of knowledge, international consensus has not yet been reached on Indigenous peoples’ rights to the protection of cultural knowledge systems, either within an intellectual property regime or through some other over-arching legislative or policy framework.

In the above mentioned article, the consensus group has outlined eight interconnected ethical principles concerning traditional Indigenous medicines used in Western psychedelic research and practice. These include:

Reverence, Respect, Responsibility, Relevance, Regulation, Reparation, Restoration and Reconciliation.

How Can We Fix It?

These core principles remind me of the discussion from the Plenary of Indigenous Leaders back at the International Drug Policy Reform Conference in the Gila River Indian Community. One of the questions that was given to the panel at Reform was, “What does Indigenous culture teach us that applies to this work?”

The work being referenced here was to drug policy reform and harm reduction, but can apply directly to the psychedelics field. Using psychedelics for healing should include the core principles and values in which their use started and by taking those out of the equations were white-washing another part of history. How as a field are we preaching collective healing when we don’t even have a basic understanding of what it means to be a collective?

Arlene Brown, founder of Crossroads Recovery Center and Skoden Native Harm Reduction Services, reminded the room that western medicine was not made for Indigenous People, the healing that is centered in western medicine is very different. Western medicine moves in a didactic course, where all information is coming from the top source, and those who have defined these values are those who will benefit from it. Indigenous medicine is circular, with each aspect being a valuable part and resource within the circle. There are lessons to be learned from more than just the doctor, it’s about listening and being open to the dynamics of existence, not just taking medicine and hoping for the best.

To fix the issue within the psychedelics field, we need to learn from what folks are doing across the harm reduction and drug policy landscape, and focus on what is actually working. For example, Brown partnered with the National Harm Reduction Coalition to create a Native-focused harm reduction toolkit, which addresses needs specific to these communities. By expanding access to resources and creating resources specifically for communities outside the ones clinical trials typically focus on, we can expand the reach and include those who have been systemically left out or hurt.

How can the psychedelic field continue on the same route and profit from Indigenous knowledge when there has been intentional systemic and institutional suffering at the hands of westernization? How can the field preach that psychedelics are going to heal trauma and make the world a better place when there is no interest in assisting these broken communities? Everyone tends to think of these atrocities in the past, but they are happening right now.

As of 2022, Native Americans have the highest rates of substance abuse and opioid overdose, compared to other ethnic groups in the US. These high numbers are also known to be underreported. Despite this, many are left to figure out how to help their own communities instead of receiving any benefit from general research or medicine. For example, there are studies assessing the therapeutic effects of natural psychedelics like ibogaine, ayahuasca and psilocybin on substance use disorders, but the recruitment does not reflect those who are being disproportionately affected by these conditions. They are not in these studies and they most likely will not receive the benefit of them if they were to become mainstream.

When psychedelics are approved, one large concern is that they will be extremely expensive and only able to be used in a specific indication as defined by the western medicine paradigm. This paradigm is typically fitting for the middle to high class, not reaching those who need it most. So, what is the plan for disseminating these treatments to the public? Will they be available to Indigenous communities? Will these communities be able to use the medicines in their way or will they have to abide by the western model?

So, how can the second wave of psychedelic research be true to its word in being a true collective? It is not enough to just say sorry or ask for forgiveness, justice must be restored and something must be done. There needs to be a paradigm shift and I think that frightens people who have benefited from the current system.

As stated at the Plenary at Reform, “Our culture says we can heal and we can restore, but it may not look the same as when you started.”

That is what people seem to forget. The shift in culture drives change and change should reflect those who have been participating in the culture. If things are to really change, we can’t sit comfortably; we have to join in on the disruption. This disruption may take different forms, it can be through calling out bad actors, lifting voices of people who have been overshadowed, it can also be in the form of being quiet, letting someone else take a turn and waiting in the other room until you’re called in.

One thing that really stood out was when one of the panelists said: it is a spiritual act to restore First People as first. We have been last for too long.

So what does that look like?

I’m going to refer back to the experts in this topic. Recently, I had the opportunity to sit alongside various experts in the psychedelic field including Indigenous South American Medicine Woman: Isa Bolivar. Her practice focuses specifically on ayahuasca and its healing properties. One thing she discussed is how the separation of medical and spiritual is more harmful than helpful. For example, in her community the doctors and shamans work together to provide a fully holistic approach to health. When someone comes with a problem they aren’t just assessed quickly and given medicine, they are spoken to with respect and care from their community. They return to potentially receive the medicine of the ayahuasca, maybe in conjunction with other treatments or with other people or maybe not at all, but there is a larger focus on the mind-body-spirit connection and determining what is best for your health. This relationship between the healers and the seeker (patient) is so important for ensuring positive outcomes in care but it’s also important because the seeker feels at ease about disclosing other medications or conditions to the healer that may affect the use of the ayahuasca. This gives the seeker autonomy over their decision to use the medicines rather than follow a western model alone.

How would it look if psychedelic medicine could develop that kind of model?

Why do these things have to exist outside of each other?

Most importantly: How do we reconcile them in a respectful and restorative way?

When we think about solutions, it is important to remember that it’s not only intellectual property and dismantling oppressive systems, it’s also about the medicines themselves. Widespread interest in psychedelics has brought the spotlight on plant medicines such as peyote (lophophora williamsii) and ayahuasca (banisteriopsis caapi), for example. This heightened interest in these psychedelics from pharmaceutical and biotech companies is becoming increasingly problematic for preservation of the ecosystems in which these plants thrive, as well as availability of these medicines for traditional use.

The commodification of these Indigenous traditions through false or ‘plastic’ shamanic practices and retreats, cultivation with large carbon footprints — see what happened with cannabis — and companies looking for a quick buck is not just inherently morally wrong, but it’s also so far removed from the whole point of these traditional practices. Another thing that was important to discuss was the use of specific plant medicines, such as ayahuasca outside of these Indigenous communities. Ayahuasca takes at least 10 years to grow in natural conditions to be ready for harvest and made into ayahuasca tea. If the vine is cut and harvested earlier or improperly, the plant no longer becomes viable for ceremonial use.

Taken together, this all comes back to some of the concepts I mentioned earlier. These ideas are representative from a variety of sources including personal conversations, the paper above mentioned, and attending talks on the topic.

Reverence — for the medicine and for the earth it comes from (specifically in terms of naturally occurring psychedelics)

Respect — of Indigenous knowledge, practice, and tradition

Responsibility — in understanding what is right and wrong; being responsible for harmful practices

Relevance — of learning and listening to Indigenous folks; decolonizing psychedelic medicine

Regulation — of specific use of plant medicine, leaving it alone for Indigenous people

Reparation — credit where credit is due including cultural, intellectual, religious and spiritual property; Give back to Native communities if you are researching/developing their plant medicine

Restoration — of Indigenous leadership across the psychedelic field

Reconciliation — First People First.

I want to point out that there is work being done in this area, it’s not all pessimistic. Chacruna Institute for Psychedelic Plant Medicines has an Indigenous Reciprocity Initiative of the Americas. This is a “community-led biocultural conservation program consisting of a network of 38 different Indigenous groups in 20 partner organizations engaged in different projects involving food & water security, agroforestry and environmental health, fighting for land rights, and building economic and educational support.” They also include a highlight of Indigenous Peoples involved in the Psychedelic Renaissance on their website which can be found here.

Still Learning, Still Growing

I’m going to end with a personal anecdote. For those who don’t know, I’m a white girl from the suburbs in MI. I went to school at Central Michigan University which sits right on the land of the Saginaw Chippewa Tribe, which is when I realized the disproportionate health adversity, though admittedly I unfortunately never got involved in learning or doing more beyond just being aware. I’ll be the first to admit that sucks.

So fast forward, I’ve become heavily involved in the psychedelic space as someone who is interested in the potential therapeutic effects of psychedelics. Being in this field, I realized I have another opportunity to be involved in learning and doing more.

So recently, I was given the privilege to organize a psychedelic-related panel for local organization Mushroom Mania, which was titled The State of Psychoactive/Entheogenic Plants and Fungi, which you can find the recording here.

Now, being tasked with choosing participants I started with my own contact list, which as I soon found out, included a lot of non-indigenous white men (a reflection of the field as a whole). Tapping into a diverse psychedelic community as an academic is difficult, even more difficult to reach and befriend folks who have been betrayed by the system in multiple ways. In my search, I really didn’t know where to start so I started with asking my co-host and moderator if they knew anyone, I posted on social media and asked my friends. While I knew my intentions were pure, I’m still learning how to navigate being an accomplice.

It is not enough to give a seat at the table, but we must form genuine relationships with the community in which we aim to include, and this must be of pure heart not just to have a token presenter. As my close friend pointed out, knowledge is a privilege not a right. And even though I wanted to be able to include someone in the conversation to whatever degree they saw fit (and I wanted to pay them damnit!), there are some things that we are not meant to know, some conversations that we are not meant to share.

In the end, after being extremely annoyed and frustrated at the lack of any form of diversity in the psychedelics field (especially on the east coast), I was able to put together a really exciting panel with a little help from my friends. This story isn’t about me, this story is to highlight that even with the best intentions, we (white folks in the field of psychedelics) need to earn trust.

The point is: it’s not just a seat at the table whenever you feel like giving it, it’s a seat at the table all the time, whenever a person is ready and able to take it.

The psychedelic field needs to remember its roots. We as researchers need to admit there are many people who know SO MUCH MORE than we do, and be open to learning from them and learning from our mistakes.

With that, I want to leave my readers with just a few folks I’ve been learning from in the last few years:

Sutton King, Afro-Indigenous and a descendent of the Menominee and Oneida Nations of Wisconsin, co-founder and President of Urban Indigenous Collective

Yuria Celidwen, descendent of Nahua and Maya Nations, researcher of Indigenous Contemplative Traditions

Marlena Robbins of the Diné Nation, doctoral student at UC Berkeley working an access to psychedelic medicines for Indigenous peoples

Sam Rivera, descendent of the Taíno People, Executive Director of OnPoint NYC

Virginia Hedrick, member of the Yurok Tribe of California and of Karuk descent, Executive Director CA Consortium for Urban Indian Health

Arlene Brown of the Bishop Paiute Tribe, founder of Crossroads Recovery Center and Skoden Native Harm Reduction Services

Gina Jackson of the Western Shoshone and Oglala Lakota Tribes, co-CEO and Co-founder of Return to the Heart Foundation

Isa Bolivar, South American, natural born Shaman and traditional energetic healer https://www.isabolivar.com/

Please feel free to reach out if you have any feedback on this article. These are expressly my own opinions and do not reflect the actual opinions of my affiliations or anyone mentioned in this article. I am aware that I do not speak for, represent the thoughts, feelings and opinions of several different First Nations and in no way was I trying to do so.

References:

1. Borrell, B. (2024) The Psychedelic Evangelist. New York Times. https://www.nytimes.com/2024/03/21/health/psychedelics-roland-griffiths-johns-hopkins.html
2. Jaster, A.M. (2023). The Psychedelic Renaissance: What is Going On? Part 1. Psychedelic Brain Science. https://www.psychedelicbrainscience.com/post/the-psychedelic-renaissance-what-is-going-on-part-1
3. Welker, J. (2023). The Religious Science of Johns Hopkins. Psychedelic Candor. https://www.psychedeliccandor.org/p/the-religious-science-of-johns-hopkins
4. Hause, S. & Maltby, W. (2001). A History of European Society. Essentials of Western Civilization (Vol. 2, pp. 245–246). Belmont, CA: Thomson Learning, Inc.
5. Evans J., Woolfe S. (2024). The Inner Healer and the Inner Critic. Ecstatic Integration. https://www.ecstaticintegration.org/p/the-inner-healer-and-the-inner-critic
6. Grof, S. (2006). When the Impossible Happens: Adventures in Non-Ordinary Realities. Sounds True, Inc. Boulder, CO 80306.
7. Love, M. (2022). Fellow Travelers: The experience of facilitating MDMA-assisted psychotherapy in the treatment of posttraumatic stress disorder. Dissertation. Wright Institute Graduate School of Psychology.
8. Celidwen, Y., Redvers, N., Githaiga, C., Calambás, J., Añaños, K., Chindoy, M. E., Vitale, R., Rojas, J. N., Mondragón, D., Rosalío, Y. V., & Sacbajá, A. (2022). Ethical principles of traditional Indigenous medicine to guide western psychedelic research and practice. Lancet regional health. Americas, 18, 100410. DOI: https://doi.org/10.1016/j.lana.2022.100410
9. Institute of Human Rights and Business (2022). What is free prior and informed consent? https://www.ihrb.org/explainers/what-is-free-prior-and-informed-consent-fpic#:~:text=Free%2C%20prior%20and%20informed%20consent%20(or%20FPIC)%20centres%20on,activities%20undertaken%20on%20their%20land.
10. Sterling, R. L. (2011). Genetic Research among the Havasupai: A Cautionary Tale. Journal of Ethics, American Medicine Association. https://journalofethics.ama-assn.org/article/genetic-research-among-havasupai-cautionary-tale/2011-02
11. Kaliszewski, M. (2024). Alcohol and Drug Abuse Among Native Americans. American Addiction Centers. https://americanaddictioncenters.org/addiction-statistics/native-americans
12. Centers for Disease Control and Prevention (2023). Opioid Overdose Prevention in Tribal Communities. National Center for Injury Prevention and Control. https://www.cdc.gov/injury/budget/opioidoverdosepolicy/TribalCommunities.html
13. George, J. R., Michaels, T. I., Sevelius, J., & Williams, M. T. (2020). The psychedelic renaissance and the limitations of a White-dominant medical framework: A call for indigenous and ethnic minority inclusion. Journal of Psychedelic Studies, 4(1), 4–15. https://doi.org/10.1556/2054.2019.015
14. Cooke, J. (2024). Beware of the Plastic Shama. Tripsitter. https://tripsitter.substack.com/p/beware-the-plastic-shaman
15. Manning, A. (2021). Insatiable demand for cannabis has created a giant carbon footprint. Colorado State University. https://engr.source.colostate.edu/insatiable-demand-for-cannabis-has-created-a-giant-carbon-footprint/
16. Meyer, M. (2021). Global ayahuasca trend drives deforestation in Brazil’s Acre state. Mongabay. https://news.mongabay.com/2021/12/global-ayahuasca-trend-drives-deforestation-in-brazils-acre-state/

Voices echoed off the walls of the auditorium as people shouted the names of people they have lost, and with each name spoken it is a reminder of the reason we were all gathered in this special place.

The International Drug Policy Reform Conference was held this past month in the Gila River Indian Community where folks came together to discuss the state of the world and how the hell we can fix it. While the topics remained broad and multidisciplinary, from discussing socioeconomic reform to psychedelic commercialization to centering indigenous voices to defunding the police and funding communities, the main takeaway is that the war on drugs in a war on people and we must use radical inclusivity and radical love to press forward.

With all of the amazing sessions that happened, there is something I think needs to be discussed on this platform, in a space that is seen by many involved in the psychedelic community and that is psychedelic exceptionalism.

As a psychedelic researcher, sometimes I find myself in the midst of the hype (yes, even me) around psychedelic policy and the freight-train that is this “movement.” There is so much swirling around us and the attempt to keep up with the science, the policy, the patents and the complaints is overwhelming. It seems the same arguments are made over and over, without any resolve and without any resolutions for the future.

The Reform conference had two main breakout psychedelic sessions and some smaller discussions in the form of community sessions, and within all of these sessions I kept finding myself wondering why we keep arguing, why the harm reductionists find the psychedelic people elitists and why the psychedelic people thing taking psychedelics makes them better than someone who takes other drugs. It’s exhausting, but these things are important for us to sit with. In the next few sections, I’m going to highlight some key takeaways I got from these sessions and leave you, the readers, with some hopeful food for thought.

The Healing Rhetoric

Psychedelics will rewire your depressed brain, expanded consciousness for all, spiritualized humanity, collective healing with psychedelics, and the ever so co-opted phrase plant medicine, are just a few slogans floating around following this renewed psychedelic renaissance.

Psychedelics are often touted as a cure to all suffering and a way to expand consciousness to become a better version of yourself or to heal, while other drug use is thought to be chaotic, dirty and only puts you in a dark place. The psychedelic movement has lent itself to exceptionalism, where the same social constructs for other drug use need not apply. This is problematic because it reduces psychedelics to being the “good drug” and anything else “the bad drug,” which is something that was seen with the rise of cannabis.

The truth is, people have different relationships with substances, and those relationships and these relationships i) don’t make anyone less of a person for their relationship and ii) is none of anyone’s business unless that person wants to share their experience. In the psychedelic space people tend to discuss how they were able to wean themselves off their pharmaceuticals like adderall or SSRIs using psychedelics and openly encourage others to do so, ignoring the fact that some folks have a positive relationship with their pharmaceuticals and demonizing them for choosing to take these “bad drugs” and not the “good drugs.”

In the first psychedelic session of the weekend, Psychedelic Decriminalization: Gateway or Hurdle to All-Drug Decriminalization, Betty Aldworth (director of communications for MAPS, formerly worked with SSDP and cannabis regulation) brings to the attention of the attendees that the drugs in and of themselves are just drugs and that it’s important to focus on the language we use to talk about these things. If we aim to educate people about any drug, we need to be expansive, not restrictive.

What I appreciated most about Aldworth is her desire to use her position at MAPS to educate people about all drug use and further reform for all drug policy, not just psychedelics. She even did air quotations around the term plant medicine. The use of plant medicine as a phrase is not only problematic from an overall harm reductionist viewpoint, but it’s also co-opting this phrase from indigenous groups (we’ll get to that next).

We need to put an end to this idea that if you are someone who uses psychedelics or plant medicines, therefore you are better than someone who does other psychoactive substances, this idea that psychedelics are “harmless” and promote “healing” while someone who uses heroin for example (also a plant medicine) is a drug user and cannot have a positive or healing relationship with their drug of choice. It also feels necessary to point out that not all psychedelics are even plants/fungi and these still have profound effects on people, for example synthetic psychedelics are being researched as anti-inflammatory agents to help those with asthma or pain.

Further, when psychedelics are constantly called healing drugs the potential negative side effects are significantly ignored, reduced or forgotten. These are powerful, mind-altering substances that just like any substance can be used chaotically or for non-healing purposes. There is plenty of evidence that psychedelic use by people who are uninterested in this healing rhetoric have no changes in their belief systems, or further validate their current belief systems which can be problematic to society and perpetuate the war on drugs. In addition, psychedelics have been used for centuries in different ways including recreationally where people have no interest in using them medically or ceremonially.

From a policy perspective, as it was pointed out by Ami Kachalia from ACLU in New Jersey, when psychedelic reform is discussed the lead is always from the healing/medicinal viewpoint, similar to medical cannabis. Not only does this reek of psychedelic exceptionalism, it also makes it difficult for other drug policy reform bills to be seen as important when they aren’t focused on healing or curing anyone. Psychedelic reform doesn’t lead with the drug, it leads with drug indication which perpetuates medicalization. In the eyes of policymakers, this may make them a little more comfortable lifting the restrictions and introducing new drug policy, but these bills often leave behind non-psychedelic substances.

In Aldworth’s response to the policy goals of psychedelics versus other drugs, she was the first to admit that psychedelic policy is not inclusive or deserving at this point. For example, psychedelic bills are focusing on only de-prioritizing mushrooms or trying to convince policy makers on their medicinal value when the time and effort could be going into bills that focus on safe drug supply for ALL drugs, decriminalization of ALL drugs, and working to free people who are wrongly incarcerated and dying in prison for personal drug use. There is some light in the convoluted policy tunnel: a bill in Denver that passed that will train 4,000 first responders on how to respond to a psychedelic-related crisis, which is typically a mental health-related crisis. The training here can be applied to a variety of other non-psychedelic situations, which hopefully leads to de-escalation and less harm caused by ill-trained responders.

As Aldworth said, “It’s important to plant our seeds to bring in others on overall drug advocacy.”

Models of Use

A continuation of thinking about the language used to describe psychedelics is the use of language to describe the models in which they are employed. The big three include medical, spiritual, and recreational.

Medicalization of psychedelics probably produces the most conversation, as it is a goal for several drug companies (MindMed, Atai Lifesciences, Compass Pathways, Cybin, etc.) and special interest groups (MAPS) to provide a legal way for people to access psychedelics for medical use. What is not often thought of, as Ifetayo Harvey of POC Psychedelics Collective, is how medicalization is used as a justification for drug reform even though the medical system has treated people who use drugs poorly for a long time, especially the POC and indigenous folks that have been systematically targeted. She so eloquently points out: If we keep trying to integrate psychedelics into the burning house, they will take on the issues of the house.

The medical system has its flaws, both major and minor, which would only be exacerbated by adding psychedelics into the mix. The medicalization of psychedelics can be two things i) the use of these substances as an “assisted therapy,” known as P-AT and ii) the configuration of a psychedelic into a pill that does not induce hallucinations and can be taken like any other pharmaceutical. The P-AT model typically consists of an on-call physician, two therapists (one must be licensed), and other staff. Sessions include preparation sessions, psychedelic sessions and sometimes integration sessions. Therapy alone is already shown to be unaffordable for a large majority due to issues with insurance coverage, premiums and general accessibility. For example, a clinic in Oregon touted a plan for “medical P-AT” that would cost people thousands of dollars and the center wouldn’t even legally be able to provide therapy, just essentially an overpaid babysitter.

So, how would this model allow access for the people who might benefit from it most if they wouldn’t be able to afford it financially or afford to spend the time? Some would argue that for psychedelics to truly work, one must be open to spending the time healing, but not everyone is equipped to quit their day job and embark on a spiritual journey. Several people who could benefit from psychedelics would benefit even greater from access to stable income, education, housing and food and some would argue that is what these organizations should be aiming to fund alongside their treatments.

This leads into the second medical model: the pharmaceutical formulation. Several companies have poured millions of dollars into attempting to isolate the therapeutic effects of psychedelics without inducing “side effects” like hallucinations, which some would argue are the effects. While this point remains important, some folks who believe the subjective effects are necessary fail to see the potential positive outcomes of pharmaceutical adaptations. For example, while cost still may remain an issue for some it would be significantly less expensive in comparison to P-AT and people would most likely be able to access medications more readily than if they were going to be going through an entire psychedelic experience. If the goal of psychedelic medicine is to truly heal people, then formulating them in a way that provides more opportunities for treatment should be welcomed.

The other side of the medicalization coin is that people are being left out of the conversation. If pharmaceutical companies and special interest groups are taking over the production of psychedelics and determining their legality, how does that affect people who still want to engage in other forms of use? Is the medical model — both types — actually going to help more people or will it end up gatekeeping psychedelics from folks who aren’t interested in this version of healing? To that end, who are we letting determine the medical models of P-AT? As Daniel Garcia from POC Psychedelics Collective points out, a large majority of funding for psychedelic research specifically for PTSD and depression comes from some potentially dangerous people including the US Department of Defense, Christian Angermayer (who served as an advisor to Rwandan Dictator Paul Kagame and now runs ATAI), and a variety of silicon valley and wall street elites (who majority support TESCREALism ideals). I will be the first to admit that it is difficult to obtain funding for these studies, especially large scale human clinical trials, but does the psychedelic movement really want to be formulated and backed by the same people who perpetuate militarization, class separation and the war on drugs? If that is where the funding is coming from, the organizations receiving it could at least spend more of their time and money fighting for basic human rights that are realistic.

Coming out of this medical framework, there is perhaps the opposite end of the spectrum of psychedelic use: ceremonial. When asked who or what was being left out of the conversation when it comes to the psychedelic renaissance, several panelists had a similar answer said in various ways: the spirit of the medicine. Since the renewed interest in psychedelics, indigenous traditional knowledge has been put to slaughter against the system. The way some psychedelics were used as sacrament or for spiritual healing has been replaced with pharmaceutical interests and development of the abovementioned medical paradigms. Even the P-AT model, which still provides some preparation and integration, is really only making the drug available within the bounds of a specific setting, removing the ceremony. There have been some attempts for the preservation of some ceremonial aspects of psychedelic use in clinical practices, but then that has also begged the question of influencing patients with religious beliefs of the prescriber and whether or not that is ethical.

Further, while some organizations such as Decriminalize Nature fight for decriminalization of all natural psychedelics (including peyote) and access for all individuals, the Native American Church aims to continue to protect peyote and the environment in which it grows from people outside Native communities. There was a lot of discussion about centering indigenous voices at Reform 2023, but when it seems to come down to it many organizations claim they want input but tend to ignore requests from indigenous groups. As Garcia so blatantly stated, “Just give the f — -ng land back,” and if it’s truly healing that you are genuinely seeking then you will be let into the circle. Respect is a large part of it. There are also alternatives that can be consumed. You can experience mescaline in synthetic form or through San Pedro cactus, which leaves the teacher plant for indigenous folks. It’s respect for the culture, the identity, the ancestral knowledge behind these sacred practices and the substance being consumed. Dr. Angela Carter brought up how putting something with such a rich history and spirit behind it into a single pull removes so much that can be gained by the experience. These kinds of substances allow people to see deeply within themselves and their past/future, allowing a person to be able to take what they have experienced and do the work to become the next version of themselves. Medical models take that away, making psychedelics seem like a one-stop shop.

The largest critique of the westernization of psychedelics is that the medical models tend to ignore things that cannot be measured or quantified. There are ailments across a variety of cultures that are not recognized by western medicine but can be potentially healed in a variety of ways including herbal medicines, meditations, breathwork, ceremonial prayer and even the use of psychedelics. These things are ignored by western medicine and by taking psychedelics into this framework, what else — or who else — will be ignored if they seek to use psychedelics in a non-medical way? There are dynamics beyond the physical that makes someone who they are and influences their choices, as well as their needs. The historical indigenous use of psychedelics and the concept of healing is circular and the people who are choosing to take this route should be a part of determining their needs. Calling the ceremonial use of psychedelics a model doesn’t even seem fitting because it’s so much more than that.

This medical hijacking rhetoric is something that I’ve heard in almost every single conversation I’ve been in about psychedelics, it made me think about the opposite: ceremonial hijacking. While allies, or accomplices as Sam Rivera from OnPoint NYC said it, is a great thing, I’ve seen time and time again the co-opting of ceremonial use of a variety of psychedelics. Whether they are starting their own healing businesses fully equipped with online or in-person courses for a fee, weekend getaways in jungle settings, claims of shamanism and more, it leaves a bad taste in my mouth. The preservation of these rituals is something that absolutely should be done, but maybe they should be done by the people who created and passed these rituals down for generations, not some guy on reddit that will take you to the jungle for $100 and give you their homemade Changa. (I’d like to note here that there are many non-indigenous folks who have spent several years studying and enriching themselves into the true culture and spirit of the medicines they are offering, these are not the people I’m calling out.)

The Right to the Human Experience

We live in this society in the US where it’s so individual and so transactional that it’s very hard to picture a world where ceremonial use of psychedelics is welcomed, where people can come together as a collective and feel something other than the pressure to survive and participate in capitalism. That’s kind of the point of the argument for the necessity of using psychedelics — or any drug — in this way. It’s a human right to experience something extraordinary.

Finally, I want to discuss the use of psychedelics outside these two settings: recreational use. This type of psychedelic use tends to fall in the sweet spot between both healing indications and is actually the most popular use of psychedelics in the modern era. Most people know the history of LSD and have heard the phrase “Turn on, Tune in, Drop Out” which was famously coined by Timothy Leary in the 1960s during the height of psychedelic recreational use. Still to this day several people, mostly in their late teens to early twenties, use psychedelics in a variety of ways including just for fun. As someone from the midwest suburbs, I always found it shocking that others were shocked at these statistics. I’ve noticed that some folks who choose to partake in drugs ceremoniously tend to be surprised with the choice of people to use psychedelics recreationally. Even Bia Labate PhD, a trained anthropologist, co-founder and Executive Director of Chacruna Institute, described being surprised upon learning how people are using some drugs in a non-ceremonial way. She then points out how despite the ways they are used substances have been a building block to civilizations and cultures around the world. It’s just part of the human experience.

Running with this idea that substances are just part of the human experience, then why do some people within different sectors of drug-related movements seem to look down on folks who don’t fit into their specific ideals? Aren’t we all fighting for the same thing: the end of a war on people and their choices, the basic human right to alter our own experiences?

It seems to be that recreational use of psychedelics is looked down upon by both the medical and ceremonial camps either for being “dangerous” or for “lacking intention” but what if sometimes the intention is just to feel something …else? I’m not discounting that psychedelics can be dangerous and should be used smartly but it should be up to the person to determine how they want to use them. The important thing is that the people engaging are educated and equipped to have that experience, which brings us full circle to harm reduction practices. With the increased use of psychedelics we should be spending more time talking to people about the potential risks (as well as the benefits) and outcomes, what can be done in those situations, and how to look out for people that are just trying to take advantage of the growing use. Psychedelic use has always been recreational and will probably continue to be recreational. If psychedelics become decriminalized or legalized fully it would allow someone to decide for themselves with all the possible information at their disposal.

Something that really hit home was a statement from Labate, “There is a multiplicity of models because we are a multiplicity of people.” This statement was followed by an analogy of how drugs are like food. There is not one particular preparation that will suit everyone’s needs. We can’t expect to serve one dish to the entire world and expect them to enjoy it, or to feel fulfilled. I think it’s important to apply this outside of psychedelics as well, remembering that everyone has their human right to bodily autonomy, which includes the substances they put in it.

Another take away from this session was the importance of honesty when it comes to these different models of psychedelics by pointing out that many of the current “medical” models appearing with the recent bouts of decriminalization are not actually approved medical models and sometimes it isn’t really even decriminalization.

To be honest, the psychedelic field could benefit from listening to voices outside of their bubble. If we truly want to move psychedelics forward as a means to help people, everyone needs to work together to develop better risk assessments for those seeking to take psychedelics, education on situational awareness and familiarity with the drugs and their side effects. We also need to have more conversations on who should be leading in this field, who is allowed to provide healing and who gets to decide what people deserve healing or why they can’t heal themselves.

Keep a watchful eye out for Part 2 in the coming weeks which will focus on indigenous leadership and intersectionality.

This was originally written and published on Psychedelicbrainscience.com 10/23/23.

The Reform Conference sat at an almost perfect intersection of research, community organizing and policy, with sessions for almost any interest. For a researcher like myself, I was excited for the sessions with the National Institute of Drug Abuse (NIDA) and I was thrilled to hear about evidence-based policy happening as a result of on the ground mobilization and community-driven research. But as an advocate, I found myself disappointed when I thought about how there could be so many more of us researchers at this conference.

Something that really stayed with me after the session with Dr. Nora Volkow, director of NIDA, was the attempts to keep science and research from becoming politicized. For so long the ivory tower of academia has taught folks to focus on the science, to do the experiments and to keep away from engaging in politics and policy change. “The evidence will speak for itself,” is something I’m sure every researcher has heard. Even in one of Dr. Volkow’s remarks, she discussed how it’s the institutions job to do the research and to inform the public about what drugs do in the brain and that itself should inform decisions. Unfortunately, policy is messy, often incremental, and highly depends on the local legislation and their knowledge on the issues.

While science should definitely remain objective and focused, there are some pitfalls to the non-politicized approach. We often we find that our research is late to the party, struggling to keep up with the trends and changes. For example, for many years funding has been focused on the opioid crisis and how to fix it. We know so much about IV self-administration, but now things are shifting and people who are using these drugs are finding alternative ways to use as a form of harm reduction. The use of inhalation as a route of administration was discussed and the Director herself admitted that the amount of knowledge we have on inhalation of certain compounds and how to make it safer is extremely limited compared to what we know about say — injecting heroin.

In addition to the lagging in funding and publishing that drive the research, there is a blatant lack of community-driven research. This refers to collaborative research that allows for people with lived experience to have a seat at the table. If the population we are trying to serve isn’t involved in the process of developing research questions, designing methods and providing insight, then are we really serving them? Or are we serving us? Is the research we are doing actually to benefit who we say it will or is it to benefit from the community and climb the ivory tower?

Whether we like it or not, research is politicized. The entire war on drugs has politicized research and funded research that focuses directly on the negative impacts of psychoactive substances while ignoring the positives. The current drug laws we have are disproportionately targeting black and brown folks, indigenous folks, as well as poor people of all races and ethnicities. The lack of research on stimulant use and cardiovascular issues following the crack epidemic (which don’t even get me started) has caused several people to lose their lives, majority of them being older black men. If you need a more recent example of the politicization of research and medicine, I’d like to remind everyone about the politics involved in the COVID vaccine.

Whether we as researchers like it or not, the work is being taken and twisted, so why not take back the narrative? Do we not have a moral responsibility to inform the public on what we’re actually doing instead of letting them be persuaded by runaway sensationalist media titles that influence the people who make the laws?

The excuse I frequently hear by colleagues about their lack of advocacy is that they don’t want their reputation tarnished. They want to remain objective, even-headed, uninvolved… but there is no reason we cannot be good scientists while also wanting our work to better inform the policy that is going to shape our future. So, if you want to an advocate, here are some things you can do:

Be an educator — That’s part of the job description anyways!

Academic experts have a role to play in the policy process due to our unique insights and experiences from the work we do. Specifically, if you research anything surrounding drugs or people who use drugs you can humanize drug use.

• Evidence-based research presented to lawmakers from the academic experts make it more credible and less biased than if a special-interest organization was to present it. Your objectivity can remain intact and even be praised.
• The fancy letters give more leverage. Credentials lend more access to people and more influence on policy. You can use your position to speak for people who have no power.
• Use your knowledge and expertise to write letters to editors in news media, in a variety of journals or send research to news media with talking points to help them understand the current landscape.
• Consider adding policy sections to your papers when submitting for publication or infusing some implications for things beyond just the research community. Talk about how the research can influence public health and provide evidence to change policy.
• Make sure that any communication outside of an academic setting is exact and succinct, with focus on the findings and implications for the drug policy without the scientific jargon.

Be an accomplice — Outreach looks good on a CV, right? Well, it can also be good for advocacy.

Starting a partnership with a community organization or an advocacy group is a great start to not only learning more about what needs to be done but you can also help educate people about ongoing research and see how your work can help them.

• Start by volunteering and learning more about the organization, build relationships and trust within the community.
• Working with groups outside the university can also help foster trust within the community that may have been harmed through the medical system.
• Being an ally/accomplice can also lead to some awesome collaborative community-driven research or inspire someone within the community to want to be a scientist! How cool is that? Drug Policy Alliance has some awesome information on community-driven research that you can access HERE
• You can also be an ally or accomplice by using your expertise to call out bad research via letters to journals and petitions. If you think something overreaching, falsified or otherwise problematic and unrepresentative of the data, use your voice!
• This could also include posting open comments regarding policy change on public forums. For example, when the DEA called for public comment on scheduling of psychedelics the research community responded and has had an unprecidented impact.

Be a resource — Don’t have time to do outreach? Go behind the scenes!

• Most of the time policy makers just don’t know what they don’t know, and you can help them fix that by reaching out about your ongoing work and how it can help the public.
• Policymakers, especially in the local legislation, are likely to be responsive because they don’t hear from academic experts often. This can give you leverage and help start a relationship.
• Show up to events like town halls or fundraising events that the elected officials are hosting, this will allow you to connect with them and learn more about the issues that they care about. It’s important to find a common ground and connect policy work with the issues they are backing and establish a relationship.
• Once a relationship is established, let them know they can contact you to ask any questions about your topics of expertise. You never know when a bill might land on their desk that you might be able to advise them on and make a difference.
• Similar to policymakers, journalists also tend to be under informed on science and will typically welcome information. Send recently published papers that they might be able to use to further evidence-based policy or news, send them brief summaries or white papers about your research as it develops to help inform them.

Be an organizer — For those who like to be more involved

Most academics are part of professional organization or associations and these typically have committees that make decisions.

• Joining a committee or organizing one within your professional organization can help build relationships with others who are interested in advocacy but may be nervous to discuss it. This can help start conversations about how research influences policy and what you can do within the organization to influence it for the better.
• You can also join organizations like DPA or Students for Sensible Drug Policy to get more involved in the advocacy around drug policy. Don’t have an org at your university? START ONE!
• Serving on commissions is another good way to get people talking about changes in drug policy and encourage evidence-based policy change. Having an expert who is passionate about advocacy can help add drug policy and research topics to the agenda. This can also encourage folks on the board to consider factors like race, gender and class into analyses.
• Organize/participate in planning relevant events and multidisciplinary panels that are open to the public. A lot of the professional associations are networks of elite folks within academia and the public can’t learn and attend these events if they are behind a paywall. Consider planning something in collaboration with an advocacy group or community organization to discuss research and evidence-based policy.

Be available — it’s the easiest thing to do

No one has the capacity to do all of these things or commit all of their time outside of their job to extra stuff, BUT there are some things you can do periodically or when you find yourself with some free time.

• Let lawmakers, community organizers and local news know you can be used as a resource if they have any questions
• Respond to news media requests when you can, this allows you to frame the research the way its intended and challenge sensationalism
• Participate in local events that are relevant to your work
• Public education events through libraries or local orgs are a great way to start

It’s all about building relationships.

If there is one thing academics are good at, it’s networking. So, use those skills to build relationships that can positively impact the community you live in and encourage others to try out advocacy.

The climate around advocacy engagement is shifting. Many young investigators are getting more involved in their community and in organizations outside of academia. Don’t get left behind, join the movement.

I’d like to thank the Drug Policy Alliance for hosting the Advocacy for Academics training session at the Reform Conference. All the information in this document is a reflection of the session and their advice on how to bridge the divide between research and policy. For more information or to host them for a training for your institution please check out the DPA Department of Research and Academic Engagement.

Alaina is involved in this DEA case as a witness and member of the SSDP Science Policy Committee.

In the last update, the DEA had decided to withdraw their proposed scheduling of phenethylamine psychedelics, DOI and DOC. This was in August 2022.

Since then the DEA and HHS have been hard at work trying to revamp their scheduling proposal. In December 2023, the DEA renewed their efforts with Docket №1156, once again proposing placement of DOI and DOC on the federal registry under Schedule I.

Similar to their first attempt, this proposed placement received 150 public comments and multiple requests for a hearing from scientists working with these substances. Two of these requests were by the same groups as before, David Heldreth of Panacea Plant Sciences and the Science Policy Committee of Students for Sensible Drug Policy (SSDP). A third group made up of scientists is being represented by Robert Rush, Esq.

In April 2024, the DEA Judge Soeffing ordered a prehearing conference for May 3, 2024 and hearing in person June 10, 2024. Due to a lawsuit by Panacea, a stay was granted indefinitely, pausing proceedings related to the scheduling.

In July 2024, the Panacea lawsuit is dismissed and thus the DEA proceedings resumed and a new prehearing date was set for July 29, 2024. Following these proceedings an official unprecedented 9-day hearing was granted for November 2024.

This hearing will be the first time since the 1980s that scientists will be directing engaging with DEA in an attempt to stop scheduling of a psychedelic substance. A similar case was heard in 1986, when Dr. Lester Grinspoon argued that phenethylamine psychedelic MDMA should be placed as Schedule III not Schedule I. Unfortunately, the DEA determined that since MDMA had no medical value via FDA approval, it did not meet criteria for schedule III. More can be read about that case here.

The witnesses include over 10 scientists that have worked with or are currently working with DOI and DOC. They argue that these substances are critical research tools for both pharmacology and neuroscience inquiries. These substances are used to ask specific questions about how serotonin receptors operate, the role of these receptors in a myriad of central nervous system functions, and how to target them therapeutically.

In the previous articles, it was discussed how the Health and Human Services (HHS) makes recommendations to the DEA. In this renewed proposal, the HHS recommendations highlighted by the DEA have not been updated in the last four years, despite new research suggesting DOI does not have abuse liability and may have properties making it a potential compound for drug development.

Placement in Schedule I will burden researchers by adding administrative hurdles to research, and reduce the number of new studies, ultimately setting back decades of research on mental health treatments.

Why is DOI so important?

1. DOI is especially important as a research chemical due to its high selectivity for specific serotonin receptors, including the 5-HT2A receptor, which is evidenced to be critical for the effects of psychedelics.
2. DOI has been used in over 900 research articles over the last two decades not only to understand psychedelics but also in research related to monoamine signaling, neuroscience, inflammatory processes, pain, etc.
3. Current DOI research is showing promising results in understanding mechanisms related to pain management and the systems involved in opioid cravings.

Why is this proposed rule so ridiculous?

The financial barriers and bureaucratic red tape associated with obtaining a Schedule 1 licence amounts to a nearly prohibitive roadblock for many laboratories. The process for a DEA license takes anywhere from 6–24 months depending on the laboratory, university and state requirements.

While DEA has made attempts to streamline this process, according to a talk at the International Society for Research on Psychedelics Meeting by Dr. Theresa Carbonaro, pharmacologist at the DEA, applications and renewals are increasing, with more applications for these licenses than ever. Given this increase in applications, if scheduling were to happen, this could cause a potential bottleneck in this process may prevent researchers from being able to continue their work. This would cause a large disruption and may potentially even halt or ruin several scientific inquiries.

Another reason aside from bureaucracy is that the DEA’s decision to schedule DOI is not based on science or facts.

DOI is not used recreationally. It has a 36-hour duration in humans, making it extremely unlikely to be used more than once. In addition, tolerance and cross tolerance within pharmacologically similar drugs prevents repeated use and use with other more common psychedelics. The DEA would argue that a single use of a substance equals abuse, but recent develops in addiction medicine highlight that this is not the case and drug use lives on a spectrum.

Another part of their argument is law enforcement seizures and fatal complications associated with DOI. According to their own data there have been exceptionally minimal seizures, of which do not prove intent to use or distribute. Further, zero fatal complications involving only DOI have been reported.

So, what’s next? Well, the group goes to court.

If you’re interested in learning more about this or hearing from the scientists and lawyers involved, check out the Your Brain on Science Podcast featuring Elijah Z. Ullman, Brett Phelps and Robert T. Rush. The podcast can be found on Spotify or Apple Podcasts: Psychedelic Brain Science.

For more reading on the topic check out these awesome articles covering the fight against the DEA to keep DOI a scientific tool:

• DEA's Move To Ban Two Psychedelics Is Challenged As A 'Disservice To Science' In Legal Filing From Student Group - Marijuana Moment
• The DEA wants to ban scientifically 'crucial' psychedelics because people might use them
• Student Group in Renewed Bid to Block DEA Psychedelics Ban

To Check out SSDP and support our efforts:

https://ssdp.org/blog/student-led-nonprofit-fights-the-dea-in-court-in-effort-to-preserve-access-to-vital-research-chemicals-with-promising-medical-potential/

On Friday August 26, 2022, the Drug Enforcement Administration withdrew proposed Schedule 1 status for 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC).

The notice states that “The Drug Enforcement Administration (DEA) is withdrawing a proposed rule that was published in the Federal Register on April 11, 2022, which proposed to place two phenethylamine hallucinogens in Schedule I of the Controlled Substances Act.”

In a previous post of mine, I talked about the recent DEA withdrawal of another proposed rule to schedule five tryptamine psychedelics. The unprecedented withdrawal of that rule happened just weeks before the original scheduled pre-hearing for DOI and DOC. The August pre-hearing was pushed back 30 days due to filing from Panacea Plant Sciences challenging the DEA not following proper procedure for posting dates publicly. Then, on August 26th, just one month before the rescheduled pre-hearing, the proposed rule was withdrawn.

The last blog we wrote about these cases focused a lot on how the DEA has the power to regulate psychedelics, but this post is going to focus more on the lack of evidence for scheduling and what these withdrawals mean for the future.

The challenging of the DEAs proposed rule came full force. The large community of researchers and students logged individual public comments, as well as as signed petitions circulated by VCU students and Michael Cunningham of Gilgamesh Pharmaceuticals. Other companies, such as Panacea Plant Sciences, filed a request for hearing. Co-chairs of the Students for Sensible Drug Policy (SSDP) Scientific Policy Council, Lindsey Galbo (Wake Forest University School of Medicine) and Elijah Ullman (Emory University) and Danny J. Lustberg, PhD, along with Anousheh Bhakti-Suroosh (Salk Institute), and Alaina Jaster (Virginia Commonwealth University) filed a motion with the DEA for a hearing on the manner to prevent the proposed Schedule 1 status from going forward.

Why do we care?

DOI is an unscheduled high affinity, high potency partial agonist for the serotonin ( 5-HT2A) receptor, that is used mainly in scientific research. DOI has been very rarely used recreationally, unlike one of it’s analogue DOM. DOI has been extensively researched for it’s pharmacology and its ability to produce measurable behaviors as a proxy of psychedelic action in animals. DOC, also on the scheduling docket, is a close derivative of DOI and DOM, but is less common.

Despite the use of DOI as an important research tool, the DEA still attempted to claim that this compound has “high abuse potential” and poses a public health concern. The evidence provided by the DEA was found to be less than substantial to justify Schedule I status.

One of the main assays used by the governing bodies to analyze drugs for scheduling is the drug discrimination task. This task has been historically considered the “golden standard” for identifying abuse potential. The paradigm involves training an animal to press a lever in response to how they “feel” when injected with a known drug, like LSD. After the animal is trained, the researcher will give the animal a different drug to see if the animal can identify whether the drug in question is similar to the one they were trained to press the lever with. The animal is not administering the drug to itself, or facilitating any rewarding stimulation by pressing the lever. They are simply just associating their response to one drug with another.

The task is more telling of how compounds are pharmacologically similar, but since the compounds typically assessed using this paradigm are already considered “drugs of abuse” by the governing bodies, there is no way for compounds to be tested in this paradigm and not be considered “drugs of abuse.”

What does this mean for the future?

Well, the optimist in all of us would like to think this victory indicates a shift in how the DEA will handle psychedelics. But it’s all going to depend on what they do next. In the statement regarding the withdraw of the proposed rule for DOI, they state they will be “publishing a new proposed rule using an amended procedure.”

What this new procedure is, we can only speculate but there are some ideas about how the DEA will go about psychedelic drug scheduling as we move forward. One huge factor to this is the Biden administration stating they are hoping to approve MDMA and Psilocybin for psychotherapy within the next two years which will be headed by a task force of government officials. This huge announcement happened around the same time the tryptamine case was thrown out. With the changing landscape on psychedelics and their medical uses we can expect some changes in policy. What could that look like?

1. Continued bifurcated scheduling of compounds like we see with medically approved compounds based off “drugs of abuse.” This is when the drugs, substances or specific chemicals used to make a preparation are classified differently depending on the “acceptablility,” whether that be medically or socially. For example: heroin is schedule I, oxycodone is schedule II, Tylenol with codeine is schedule III and tramadol is schedule IV, but they are all classified as opioids. That is a perfect example of this scheduling concept.
2. Placing psychedelics and new schedules in schedule IV. This would be optimal because this lends to the idea that these compounds have medicinal value and have low potential for abuse. While DOI and DOC are not approved for medical use, but neither is etizolam, a compound related to benzodiazepines. Psilocybin has also been predicted to be put into Schedule IV, so this would be consistent.
3. The DEA comes back with the amended procedure, that could quite possibly have what they consider more evidence to schedule compounds at schedule I as originally proposed. This is probably unlikely because the current positive publicity for psychedelics and backing by congress and government officials would make severe scheduling and therefore the DEA very unpopular and not highly favored.

New Language Moving Forward

Something to think about in the coming days, weeks, months or even years moving forward is how we talk about drugs. The current process of scheduling drugs and the CSA relies heavily on the assumption that all drugs are drugs of abuse and all drugs of abuse are bad.

But aren’t medicines drugs and aren’t medicines good? Why is alcohol and nicotine socially acceptable but heroin and cocaine aren’t? Why are psychedelics in the same schedule as heroin? Why hasn’t THC (cannabis) been rescheduled knowing it has medical use?

There is a movement to talk about how people use drugs and how we talk about folks experiencing addiction. There are people who use drugs recreationally, spiritually and medicinally without any problems with addiction, but there are a subset of folks who fall victim to substance use disorders. While the use of drugs is always a choice, sometimes the brains response to drugs and a combination of genetic and environmental factors produce susceptibility to developing an addiction, which then becomes problematic to the persons quality of life. The use, misuse and abuse of substances is shifting to be thought of more as a spectrum rather than a black and white concept. If you asked 5 people today what the difference between use, misuse and abuse is, they would most likely all have a different answer. This lack of definition or understanding of drug use as a continuum can cause issues with policy because one policy maker may think that misuse only represents those who use prescriptions off-label, one may consider recreational drug use as misuse and addiction as abuse, while another may consider any non-socially acceptable drug use as abuse.

In order to form better and cohesive policy that is evidence-based, the scientific community needs to work with the public to inform policy makers on proper language.

In Conclusion

We have been successful for now in deterring the DEA from further scheduling multiple psychedelics this year. That is something to celebrate! But we must keep in mind, there is a long way to go to fully reform how drug policy and regulation is handled in America. If you are interested in advocating for better policy check out your local area for organizations or consider forming a chapter of Students for Sensible Drug Policy, Students for Safe Drug Use, Decriminalize Nature or Drug Policy Alliance groups.

On January 14, 2022 the Drug Enforcement Agency (DEA) proposed the scheduling of five hallucinogenic tryptamine compounds as Schedule I. This proposed rule was withdrawn on Wednesday July 27, 2022. The rule was challenged on many fronts: litigation by Matt Zorn, companies Tactogen Inc. and MindState Labs represented by Graham Pechenik, Panacea Plant Sciences CEO David Heldreth, and researchers Hamilton Morris and Jason Wallach represented by John T. Hunter.

The main argument surrounding this proposed rule was questioning whether the analysis supporting the proposal may be deemed to be, “arbitrary, capricious, contrary to law, or lack[ing] substantial evidence.”

Many others also came forward and requested hearings, logged public comments and provided testimony in the case stating that the compounds in question don’t have abuse liability, and that scheduling them would impede promising research into their potential as therapeutic or tools to understand the brain.

The DEA stated that they have “determined that it is appropriate to submit a new request to HHS for an updated scientific and medical evaluation and scheduling recommendation for these substances.” This means that for now, these substances can be researched freely, but the DEA can try to schedule them again at a later date.

On May 2, 2022 the DEA proposed the scheduling of DOC/DOI, two phenethylamine psychedelic compounds, as Schedule I. In a similar fashion, there was an outcry by scientists, advocates and others surrounding this proposed rule.

Several people logged public comments and multiple groups of scientists and activists filed petitions with 30+ signatures, with large efforts by Michael Cunningham co-founder of Gilgamesh Pharmaceuticals, Elijah Ullman and Lindsay Galbo from Students for Sensible Drug Policy, and Harrison Elder, a PhD student from Virginia Commonwealth University. A pre-hearing to present testimonial statements and challenge this proposed rule is set to take place September 30th, 2022 with challengers including a group led by Ullman and Galbo that includes Dr. David Nichols — who has challenged the DEA in regards to scheduling DOI previously. Panacea Plant Sciences CEO David Heldreth will also be at the pre-hearing following a separate request for hearing.

So all of this begs the question, why is the DEA suddenly attacking psychedelics?

What is the Controlled Substances Act?

It goes back to the 1970s, specifically 1971. The controlled substances act is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain narcotics, stimulants, depressants, hallucinogens, anabolic steroids, and other chemicals is regulated. Basically, it’s how the government decides which drugs are “bad” and which drugs are “good” based on a few things.

The scheduling goes from V to I, with Schedule I being the most regulated. Schedule I compounds have no accepted medical use and high potential for abuse. Examples listed on the DEA’s website include MDMA, LSD, heroin, and marijuana. The difference between Schedule I and II, is that Schedule II compounds are known to have some medical value, including those drugs considered more dangerous like fentanyl, methamphetamine and cocaine. So what determines which drug goes in what level?

The 8 factors for scheduling drugs:

These factors are how the Human Health and Services (HHS) analyzes substance to determine their placement on the Controlled Substances Act. The HHS then sends recommendation to the DEA based on the current existing evidence and the DEA decides whether or not to propose a placement of substance.

Paperwork and Obligations

You may have noticed that cannabis is a schedule I compound, despite the Food and Drug Administration (FDA) approving two THC-based medications, dronabinol (Marinol®) and nabilone (Cesamet®). Both of these medications are prescribed in pill form for the treatment of nausea in patients undergoing cancer chemotherapy and to stimulate appetite in patients with wasting syndrome due to AIDS. That sounds like approved medical use to me!

In 2020, there was a petition to reschedule cannabis to a Schedule II standing, but this was dismissed by the DEA. Petitioners asked for a formal process including public comment and hearings similar to proposed rule for scheduling new compounds, but they were denied. The federal appeals court denied this as well, suggesting that “petitioners failed to exhaust their administrative remedies with the DEA.” The process for rescheduling is rigorous and involves several steps, including analyses of current scientific literature and evidence, and a whole lot of paperwork. There has been very times where the DEA has rescheduled a compound. For example, in 2014 they rescheduled hydrocodone combination products, the opioid prescription pain medications, from schedule III to schedule II following the increase in opioid addiction following the popularization of these compounds.

As for the case of DOI, one of the main reasons the DEA is attempting to schedule it is “to enable the United States to meet its obligations under the 1971 Convention on Psychotropic Substances.” This is a United Nations treaty designed to control psychoactive drugs such as amphetamine-type stimulants, barbiturates, benzodiazepines, and psychedelics. By not scheduling DOI, the United States is technically not in accordance with the Convention. This treaty is one of the major reasons that drugs most likely will never be unscheduled.

Gatekeeping what is and is not beneficial

You may have heard of a term called “The War on Drugs.” It’s the longest standing war on American soil and it’s been threatening the freedom and pursuit of happiness of folks for years.

Before America was ever formed, the use of psychoactive and mind-altering substances occurred for a variety of reasons in cultures around the world. Native American tribes have used these compounds for thousands of years, whether it was peyote as sacred sacrament, tobacco leaves for meditation and clarity, to the use of psilocybin mushrooms for visions. Other cultures in Asia and India also used plants and plant medicines to induce altered states of consciousness, such as opium from poppy plants.

So how did we end up here? In a place where the government is regulating what individual and collective cultures decide is or is not beneficial for them? That answer is extremely complicated, but according the US it was to battle against illegal drug trade and help prevent people from becoming addicted to drugs. They only later realized that they could use the War on Drugs to justify racism and classist ideals, targeting the black and poor during the so-called crack cocaine epidemic and even before with “reefer madness.” The War on Drugs has allowed the government and corporations to profit off of cheap labor funneled through the prison industrial complex, and further their power into deciding which drugs are “bad” and which drugs are “good.” The good drugs usually consist drugs that are socially acceptable (caffeine, alcohol, nicotine) and the bad drugs usually consist of drugs that have negative connotations brought on by scare tactics, poor education and problematic legislation (heroin, cannabis, methamphetamine).

Back to psychedelics…

Psychedelics were originally scheduled in 1971 following the popularized use in the hippie counterculture and failure of the CIA to use these compounds as weapons. The DEA’s continued reasoning to keep psychedelics as schedule I substances and keep scheduling new ones doesn’t make any sense given the current climate in research.

Literally the day before the announcement to schedule the tryptamines, the National Institutes of Health (NIH) were hosting a government sponsored titled, “Psychedelics as Therapeutics.” At this workshop, research scientists from around the world presented groundbreaking evidence for the use of psychedelics to treat mental health issues, substance use disorders and understand consciousness. But yet, here we are.

The basis of the decision for the ongoing battle with the DEA and psychedelic regulation comes from a long history of misunderstanding scientific evidence surrounding these compounds. The War on Drugs plays a huge role in this, but we’re going to end with three points:

1. Psychedelics have not been properly investigated to assess abuse liability, widely used animal models have not reliably showed any abuse liability of classical psychedelics. Anecdotal reports of use in humans exist, but recreational use of psychedelics should not be classified as “abuse.”
2. The medical use of certain psychedelics has been used for thousands of years and has been recently evidenced by several clinical and preclinical studies, these are just not “acceptable” to the DEA. The FDA has even granted special considerations for some the indications of psychedelics.
3. Scheduling of compounds, especially has Schedule I, prohibits further investigation into the 8 factors that the DEA uses to schedule substances in the first place. The scheduling of compounds doesn’t make them any less used, it just makes them more difficult to understand and learn from.

If you’re interested in this topic and want to hear from some of the folks involved in the tryptamine and DOI scheduling battle against the DEA, you can listen to a panel that took place in August 2022. An update on the DOI scheduling will be posted as Part 2!

References & Links:

The Drug Enforcement Agency listens to psychedelic experts: https://www.drugscience.org.uk/dea/

Inside the Challenge to DEA’s Proposed Scheduling of 5 Psychedelic Tryptamines: https://psychedelicalpha.com/news/inside-the-challenge-to-deas-proposed-scheduling-of-5-psychedelic-tryptamines

DEA notice for DOI/DOC scheduling: https://ehs.ucla.edu/news/april-dea-updates-placement-doi-and-doc-schedule-i

DEA notice of withdrawal of proposed rule against 5 tryptamines: https://ehs.ucla.edu/news/federal-register-notice-withdrawal-proposed-rule-placement-schedule-i-4-hydroxy-nn

Information on drug scheduling:https://www.dea.gov/drug-information/drug-scheduling

https://www.ncbi.nlm.nih.gov/books/NBK574544/

The fight for rescheduling of cannabis: https://www.vox.com/2014/9/25/6842187/drug-schedule-list-marijuana, https://www.marijuanamoment.net/court-dismisses-dea-marijuana-rescheduling-case-but-judge-says-cannabis-reclassification-may-be-coming-anyway/

Spiritual, medicinal and recreational use of plants: https://www.science.org/content/article/did-ancient-mesopotamians-get-high-near-eastern-rituals-may-have-included-opium

https://cswr.hds.harvard.edu/news/native-american-church/2021/10/14

https://aldianews.com/en/culture/heritage-and-history/shrooms-have-history

The War on Drugs:

https://drugpolicy.org/issues/brief-history-drug-war

https://www.brennancenter.org/our-work/analysis-opinion/race-mass-incarceration-and-disastrous-war-drugs

https://www.aclu.org/other/race-war-drugs

This happens all the time in psychedelic research. For example, a study earlier this year from a prominent research group at Imperial College London and University California San Francisco, titled “Increased global integration in the brain after psilocybin therapy for depression” really stirred the pot. A news report from UCSF highlighting the research and sharing information with the lay public titled their article “Psilocybin Rewires the Brain for People with Depression” which gets picked up by other news outlets and misinforms the public about the findings and ignores the nuances in the research. It’s like a game of telephone where the information gets more and more simplified as it gets passed down.

Recently, a review came out titled “The serotonin theory of depression: a systematic umbrella review of the evidence” which challenged the current belief held by researchers, doctors and the public that depression is linked brain abnormalities relating to serotonin neurotransmission. Serotonin is a chemical in the brain that has effects on several brain systems and other chemicals, therefore influencing mood, sleep, hunger, cognition and more. The review claims that there is no empirical evidence to support this theory, going as far as to state:

“…this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti- depressant medication and may discourage people from dis- continuing treatment, potentially leading to lifelong dependence on these drugs.”

Interestingly, the only alternative theory offered by these authors is that anti-depressants are placebo or “zombie” pills (yes they actually said zombie pills). The criteria in place for the review are based specifically on the authors own set of parameters of what constitutes proper analyses, adequate addressing of confounding anti-depressant use, outcome specification and publication bias (among other things like sample size and heterogeneity). The authors did not include any clinical data assessing the effects of various anti-depressants versus placebo controls (Arroll 2009 review does a great job assessing these results).

Why does this matter?

Well, the study basically is telling people that this theory is fake and their anti-depressant medications don’t work, despite their being people with various forms of anxiety and depression that have greatly benefited from these drugs. The study also ignores the complexity of the human brain and all its interactions. Depression is thought to be heterogeneous disorder with potentially multiple underlying causes, of which anti-depressants may target some of the symptoms.

Upon being shared to the public, there have already been multiple over-simplified and sensationalized articles that can disseminate false information to people seeking professional or medical help. Even a simple google search of serotonin and depression yielded 5 news articles spreading misinformation.

This can be extremely harmful to patients and may even encourage patients to stop taking their medication, which can cause serious physical and mental side effects. We encourage everyone to look at these types of articles with a critical eye and ask the hard questions when it comes to media portrayal of science.

We also encourage people on psychiatric medication to please consult their doctors and therapists before discontinuing medication. Treatment for mental health is personalized, everyone has their own unique brain, so what works for someone may not work for you.

Check out some links below for the articles and further reading on the topic:

• https://www.sciencemediacentre.org/expert-reaction-to-a-review-paper-on-the-serotonin-theory-of-depression/
• https://www.nature.com/articles/s41380-022-01661-0
• https://core.ac.uk/reader/20449177?utm_source=linkout
• https://www.ucsf.edu/news/2022/04/422606/psilocybin-rewires-brain-people-depression
• https://www.nature.com/articles/s41591-022-01744-z
• https://academic.oup.com/hmg/article/29/R1/R10/5860824